Abuse Liability for Five Modern Oral Nicotine Products

NCT ID: NCT07132814

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-15

Study Completion Date

2026-08-31

Brief Summary

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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

Detailed Description

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Cigarette smokers of (only) filtered menthol and/or non-menthol cigarettes naïve to smokeless tobacco products (ST) and/or modern oral tobacco (MO) products and smokers also using ST and/or MO will be recruited into this AL study to evaluate elements of AL of five modern oral nicotine products (hereinafter, Study IPs) compared to combustible cigarettes (CC) only (Arm 1) and combustible and and nicotine polacrilex gum (Arm 2). An attempt will be made for at least one-third of the study population to include smokers using ST and/or MO for each arm.

Potential participants will complete a pre-screening telephone interview. They will complete a Screening Visit to assess their eligibility within 45 days prior to check-in and enrollment.

Starting on check in day (Day -1), participants will check-in at the clinical site to complete procedures to confirm eligibility. Eligible participants will be enrolled, randomized and confined for 6 days (5 nights).

Participants will be randomized to a product use sequences (using a Williams Design) in which they will evaluate one IP in each of four separate Test Sessions, such that each participant will evaluate four IPs; Arm 1: Product C (8 and 12 mg), Product D 4 mg, and a high-AL comparator (participant's usual brand \[UB\] cigarette) or (Arm 2): Product B 8 mg, Product C 8 mg, a high-AL comparator (participant's usual brand \[UB\] cigarette), and a low-AL comparator (a commercially available nicotine replacement therapy \[NRT\] nicotine gum).

On Day 1 and continuing through Day 4 for both study arms, participants will participate in Test Sessions that will last approximately 4 hours. Each Test Session will include collection of both types of PD measures (subjective and physiological) and PK measures prior to, during, and following IP use. Following each test session, used IP will be collected, stored at -20°C, and shipped to a laboratory of the sponsor's choosing.

For both study arms, on the half day prior to each respective Test Session, a Product Acclimation Period will allow participants ad libitum use of the subsequent IP (at least two trial uses) as per randomized sequence for product acclimation prior to use in the next day's Test Session. Participants can also use their UB cigarettes ad libitum, until the 12-hour tobacco and nicotine abstinence period begins prior to each Test Session, as long as the minimum use requirement for randomized IP is met. Used IP from each of the Product Acclimation periods will be collected, stored at -20°C, and shipped to a laboratory of the sponsor's choosing.

Safety will be monitored throughout the study by the Principal Investigator (PI) (or designee) by assessing adverse events (AEs), vital sign measurements, physical examinations (including an oral examination), and clinical laboratory tests.

The Medical Monitor will be available for consultation during the duration of the study and for any follow-ups after study discharge.

Conditions

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Smoking Behaviors Tobacco Use Tobacco Smoking Smoking

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Arm 1

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.

Group Type EXPERIMENTAL

Product A

Intervention Type OTHER

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

Product B

Intervention Type OTHER

8 mg nicotine oral product

Product C

Intervention Type OTHER

12 mg nicotine oral product

Product D

Intervention Type OTHER

6 mg nicotine oral product

Arm 2

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.

Group Type EXPERIMENTAL

Product A

Intervention Type OTHER

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

Product E

Intervention Type OTHER

8 mg nicotine oral product

Product F

Intervention Type OTHER

8 mg nicotine oral product

Product N

Intervention Type OTHER

Nicorette® White Ice Mint 4 mg nicotine polacrilex gum

Interventions

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Product A

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

Intervention Type OTHER

Product B

8 mg nicotine oral product

Intervention Type OTHER

Product C

12 mg nicotine oral product

Intervention Type OTHER

Product D

6 mg nicotine oral product

Intervention Type OTHER

Product E

8 mg nicotine oral product

Intervention Type OTHER

Product F

8 mg nicotine oral product

Intervention Type OTHER

Product N

Nicorette® White Ice Mint 4 mg nicotine polacrilex gum

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Able to read, understand, and willing to sign an informed consent form (ICF) and complete questionnaires written in English.
2. Generally healthy males or females, 21 to 60 years of age, inclusive, at the time of consent.
3. Smokes combustible, filtered, non-menthol or menthol cigarettes, 83 mm to 100 mm in length as primary source of tobacco.
4. 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.
5. 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.
6. 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.
7. Expired breath carbon monoxide (ECO) level is ≥ 10 ppm and ≤ 100 ppm at Screening.
8. Positive urine cotinine test (e.g., \>200 ng/mL) via dipstick at Screening.
9. 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" .
10. Willing to use the UB cigarette, Study IPs, and Nicorette® nicotine gum (Arm 2 only) during the study period.
11. Willing to abstain from tobacco and nicotine use for at least 12 hours prior to the start of each of four Test Sessions.
12. 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:
1. Surgical sterilization (hysterectomy, bilateral tubal ligation/occlusion, bilateral oophorectomy, bilateral salpingectomy);
2. physical barrier method (e.g., condom, diaphragm/sponge/cervical cap) with spermicide;
3. non-hormone releasing intrauterine devices (IUD) or hormone-releasing IUDs (e.g., Mirena or Kyleena);
4. vasectomized partner; or
5. post-menopausal and not on hormone replacement therapy.
13. Agrees to an in-clinic confinement of five days (four nights).

Exclusion Criteria

1. Allergic to or cannot tolerate mint or wintergreen flavoring agents.
2. Individuals or their family members that have ongoing litigation with tobacco company(ies).
3. 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.
4. 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.
5. History, presence of, or clinical laboratory test results indicating diabetes.
6. 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.
7. History or presence of bleeding or clotting disorders.
8. 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.
9. 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.
10. Weight of ≤ 50.0 kg at screening or at check-in.
11. Hemoglobin level is \< 12.5 g/dL for females or \< 13.0 g/dL for males at Screening.
12. Females who have a positive pregnancy test, are pregnant, breastfeeding, or intend to become pregnant during the course of the study.
13. Has positive urine drug screen (UDS) or alcohol test (urine or breath) at Screening or at Check-in to the Assessment Phase (Day -1), with the exception of positive results for tetrahydrocannabinol (THC). If positive for THC at check-in (Day -1), a cannabis intoxication evaluation will be performed, and inclusion will be at the discretion of an investigator.
14. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV).
15. 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.
16. 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.
17. Any use of daily aspirin (≥ 325 mg) or any use of other anticoagulants.
18. Individuals ≥ 35 years of age currently using systemic, testosterone, estrogen-containing contraception or hormone replacement therapy.
19. Whole blood donation or lost blood or blood products in excess of 500 mL within 8 weeks (≤ 56 days) prior to signing the informed consent and between Screening and check-in Day -1.
20. Plasma donation within (≤) 7 days prior to signing the informed consent and between Screening and check-in Day -1.
21. Employed by a tobacco or nicotine company, the study site, or handles raw, unpackaged tobacco- or nicotine-containing products as part of their job.
22. Has used an investigational drug, device, biologic, or tobacco/nicotine product in a previous clinical study within 30 days or 5 times the half-life of the product (whichever is longer) prior to Screening.
23. Drinks more than 21 servings of alcoholic beverages per week.
24. Determined by an investigator to be inappropriate for this study.
Minimum Eligible Age

21 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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RAI Services Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brian Keyser

Role: STUDY_DIRECTOR

Reynolds American

Locations

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Dr. Vince Clinical Research

Overland Park, Kansas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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John Darnell

Role: CONTACT

Phone: 3367410386

Email: [email protected]

Kristen Prevette

Role: CONTACT

Phone: 3367411873

Email: [email protected]

Facility Contacts

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Patricia Deluca

Role: primary

Other Identifiers

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CSD252401

Identifier Type: -

Identifier Source: org_study_id