CClinicalTrials.gg
CompletedNCT06777784Updated Dec 23, 2025

Modern Nicotine Oral Product Abuse Liability

An interventional study of Product A and Product B in Smoking and Tobacco Use, sponsored by RAI Services Company. Completed at 2 sites in United States. Open to participants aged 21 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-12-23.

Sponsored by RAI Services Company · Not applicable, Interventional, and Other

Phase
Not applicable
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
21 Years to 60 Years
Sex
All
01

Study summary

This is a two-site, open-label, randomized, 8-way 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.

Read the detailed description

Cigarette smokers naïve to smokeless tobacco products (ST) and smokers also using ST will be recruited into this AL study to evaluate elements of AL of six modern oral nicotine products compared to combustible cigarettes (CC) and nicotine polacrilex gum. An attempt will be made for at least one-third of the study population to include smokers using ST.

Potential subjects 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), subjects will check-in at the clinical site to complete procedures to confirm eligibility. Eligible subjects will be enrolled, randomized and confined for 10 days (9 nights). Prior to the first product acclimation period, subjects will conduct a product familiarization of three of the modern oral nicotine products. Subjects will be randomized to one of eight product use sequences (using a Williams Design) in which they will evaluate one IP in each of eight separate Test Sessions, such that each subject will evaluate eight IPs, including six modern oral nicotine products, and both a high-AL comparator (subject's usual brand [UB] cigarette) and a low-AL comparator (a commercially available nicotine replacement therapy [NRT] nicotine gum).

On Day 2 and continuing through Day 9, subjects 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.

On the half day prior to each respective Test Session, a Product Acclimation Period will allow subjects 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. Subjects 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.

02

Conditions studied

  • Smoking
  • Tobacco Use
03

In context

Smoking

268 studies on the registry are indexed under Smoking; 136 are open to participants now.

This study's enrollment of 40 is below the median of 120 across 211 interventional studies indexed under Smoking.

Browse Smoking studies →

Lead sponsor

RAI Services Company is the lead sponsor of 48 studies on the registry; 10 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
21 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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 the 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 subject.
  7. Expired breath carbon monoxide (ECO) level is ≥ 10 ppm and ≤ 100 ppm at Screening and at check-in (Day -1).
  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" (Heatherton et al., 1991).
  10. Willing to use the UB cigarette, Velo PLUS IPs, and Nicorette® nicotine gum 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 eight 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: a) Surgical sterilization (hysterectomy, bilateral tubal ligation/occlusion, bilateral oophorectomy, bilateral salpingectomy); b) physical barrier method (e.g., condom, diaphragm/sponge/cervical cap) with spermicide; c) non-hormone releasing intrauterine devices (IUD) or hormone-releasing IUDs (e.g., Mirena or Kyleena); d) vasectomized partner; or e) post-menopausal and not on hormone replacement therapy.
  13. Agrees to an in-clinic confinement of ten days (nine nights).

Exclusion criteria

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 subject 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 ≤ 110 pounds 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.
05

Study design

Phase
Not applicable
Primary purpose
Other
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    Product usage order ANBGCFDE

    Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

    Other: Product A · Other: Product B · Other: Product C · Other: Product D · Other: Product E · Other: Product F · Other: Product G · Other: Product N

  • Experimental
    Product usage order BACNDGEF

    Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

    Other: Product A · Other: Product B · Other: Product C · Other: Product D · Other: Product E · Other: Product F · Other: Product G · Other: Product N

  • Experimental
    Product usage order CBDAENFG

    Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

    Other: Product A · Other: Product B · Other: Product C · Other: Product D · Other: Product E · Other: Product F · Other: Product G · Other: Product N

  • Experimental
    Product usage order DCEBFAGN

    Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

    Other: Product A · Other: Product B · Other: Product C · Other: Product D · Other: Product E · Other: Product F · Other: Product G · Other: Product N

  • Experimental
    Product usage order EDFCGBNA

    Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

    Other: Product A · Other: Product B · Other: Product C · Other: Product D · Other: Product E · Other: Product F · Other: Product G · Other: Product N

  • Experimental
    Product usage order FEGDNCAB

    Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

    Other: Product A · Other: Product B · Other: Product C · Other: Product D · Other: Product E · Other: Product F · Other: Product G · Other: Product N

  • Experimental
    Product usage order GFNEADBC

    Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

    Other: Product A · Other: Product B · Other: Product C · Other: Product D · Other: Product E · Other: Product F · Other: Product G · Other: Product N

  • Experimental
    Product usage order NGAFBECD

    Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

    Other: Product A · Other: Product B · Other: Product C · Other: Product D · Other: Product E · Other: Product F · Other: Product G · Other: Product N

Interventions

  • OtherProduct A

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

  • OtherProduct B

    Modern Nicotine Oral Product Cool Mint 6 mg Nicotine

  • OtherProduct C

    Modern Nicotine Oral Product Cool Mint 12 mg Nicotine

  • OtherProduct D

    Modern Nicotine Oral Product Cool Mint 15 mg Nicotine

  • OtherProduct E

    Modern Nicotine Oral Product Smooth 6 mg Nicotine

  • OtherProduct F

    Modern Nicotine Oral Product Wintergreen 6 mg Nicotine

  • OtherProduct G

    Modern Nicotine Oral Product Dragon Fruit 6 mg Nicotine

  • OtherProduct N

    Nicorette® White Ice Mint 4 mg nicotine gum

06

What researchers measure

Primary outcomes

  1. AUECPL 5-240

    area under the effect curve (AUEC) for PL (VAS score-versus-time)

    Time frame: 5 minutes to 240 minutes

  2. Emax PL

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

    Time frame: 240 minutes

07

Study locations

2 sites
  • AMR Lexington
    Lexington, Kentucky 40509, United States
  • AMR Knoxville
    Knoxville, Tennessee 37920, United States
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 23, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06777784
Lead sponsor
RAI Services Company
Responsible party
Sponsor
First posted
Jan 16, 2025
Start date
Feb 3, 2025
Primary completion
Mar 5, 2025
Completion
Mar 5, 2025
Last update
Dec 23, 2025

Study contacts

Brian Keyser, PhD
study director · Reynolds American

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.

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