Abuse potential of five modern oral nicotine products

An In-Clinic Confinement Study to Assess Elements of Abuse Liability for Five Modern Oral Nicotine Products

This will test how five modern oral nicotine products compare with cigarettes and nicotine gum in how satisfying they feel and how much nicotine adult smokers absorb.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 21 Years to 60 Years
• Sex: All
• Sponsor: RAI Services Company (Industry-sponsored)
• Locations: 1 site (Overland Park, Kansas)
• Trial ID: NCT07132814 on ClinicalTrials.gov

What this trial studies

This open-label, randomized, crossover study confines eligible adult smokers for six days and has each participant try four different investigational oral nicotine products in separate test sessions. The trial measures subjective effects and physiological responses (pharmacodynamics) and plasma nicotine uptake (pharmacokinetics) during ad libitum use to characterize abuse liability. Participants include smokers who are naive to smokeless/modern oral products and those who also use them, with at least one-third of participants expected to have current smokeless/oral product use. Two arms compare product sets against a high-abuse comparator (the participant's usual-brand cigarette) and, in one arm, a low-abuse comparator (nicotine gum).

Who should consider this trial

Good fit: Adults aged 21–60 who smoke filtered menthol or non-menthol combustible cigarettes as their primary tobacco source, smoke at least 10 cigarettes per day for ≥6 months, and can stay confined at the clinical site for the study period are ideal candidates.

Not a fit: Non-smokers, light smokers (<10 CPD), exclusive e-cigarette users, people outside the 21–60 age range, pregnant individuals, and those unable to be confined for the visit period are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could help identify oral nicotine products that are less likely to lead to strong dependence or that may serve as lower-abuse alternatives to cigarettes.

How similar studies have performed: Previous crossover pharmacokinetic/pharmacodynamic studies comparing cigarettes, oral nicotine products, and NRT have been done and shown measurable differences in subjective effects and nicotine uptake, so the approach is established though products tested are newer.

Eligibility criteria

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.

Where this trial is running

Overland Park, Kansas

• Dr. Vince Clinical Research — Overland Park, Kansas, United States (Recruiting)

Study contacts

• Study coordinator: John Darnell

Conditions Smoking; Smoking Behaviors; Tobacco Use; Tobacco Smoking