NCT07685795

Brief Summary

This is a single-site, open-label, randomized, 6-way crossover study designed to evaluate elements of abuse liability (AL) including subjective effects, physiological measures (pharmacodynamics \[PD\]), and plasma nicotine uptake (pharmacokinetics \[PK\]) during controlled monitored use and following ad libitum use of the study investigational products (IPs) by generally healthy smokers who are also users of smokeless tobacco.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
6mo left

Started Jul 2026

Shorter than P25 for not_applicable

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress8%
Jul 2026Jan 2027

First Submitted

Initial submission to the registry

June 29, 2026

Completed
7 days until next milestone

First Posted

Study publicly available on registry

July 6, 2026

Completed
9 days until next milestone

Study Start

First participant enrolled

July 15, 2026

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 15, 2026

Expected
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2027

Last Updated

July 6, 2026

Status Verified

June 1, 2026

Enrollment Period

2 months

First QC Date

June 29, 2026

Last Update Submit

June 29, 2026

Conditions

Outcome Measures

Primary Outcomes (2)

  • AUECPL 5-60

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

    5 minutes to 60 minutes

  • Emax PL

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

    60 minutes

Study Arms (6)

Product usage order ASDECB

EXPERIMENTAL

Subjects will use each of the 6 products during an evaluation period, followed by a 1 hour Test Session and a 7 hour ad lib session

Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigaretteOther: Wintergreen (fleece A), 12 mg nicotineOther: Wintergreen (fleece A), 9 mg nicotineOther: Wintergreen (fleece B), 9 mg NicotineOther: Watermelon Mint (fleece A), 9 mg NicotineOther: UB moist snuff (UB MST), either loose or portioned (pouched).

Product usage order BAESDC

EXPERIMENTAL

Subjects will use each of the 6 products during an evaluation period, followed by a 1 hour Test Session and a 7 hour ad lib session

Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigaretteOther: Wintergreen (fleece A), 12 mg nicotineOther: Wintergreen (fleece A), 9 mg nicotineOther: Wintergreen (fleece B), 9 mg NicotineOther: Watermelon Mint (fleece A), 9 mg NicotineOther: UB moist snuff (UB MST), either loose or portioned (pouched).

Product usage order CBSAED

EXPERIMENTAL

Subjects will use each of the 6 products during an evaluation period, followed by a 1 hour Test Session and a 7 hour ad lib session

Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigaretteOther: Wintergreen (fleece A), 12 mg nicotineOther: Wintergreen (fleece A), 9 mg nicotineOther: Wintergreen (fleece B), 9 mg NicotineOther: Watermelon Mint (fleece A), 9 mg NicotineOther: UB moist snuff (UB MST), either loose or portioned (pouched).

Product usage order DCABSE

EXPERIMENTAL

Subjects will use each of the 6 products during an evaluation period, followed by a 1 hour Test Session and a 7 hour ad lib session

Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigaretteOther: Wintergreen (fleece A), 12 mg nicotineOther: Wintergreen (fleece A), 9 mg nicotineOther: Wintergreen (fleece B), 9 mg NicotineOther: Watermelon Mint (fleece A), 9 mg NicotineOther: UB moist snuff (UB MST), either loose or portioned (pouched).

Product usage order EDBCAS

EXPERIMENTAL

Subjects will use each of the 6 products during an evaluation period, followed by a 1 hour Test Session and a 7 hour ad lib session

Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigaretteOther: Wintergreen (fleece A), 12 mg nicotineOther: Wintergreen (fleece A), 9 mg nicotineOther: Wintergreen (fleece B), 9 mg NicotineOther: Watermelon Mint (fleece A), 9 mg NicotineOther: UB moist snuff (UB MST), either loose or portioned (pouched).

Product usage order SECDBA

EXPERIMENTAL

Subjects will use each of the 6 products during an evaluation period, followed by a 1 hour Test Session and a 7 hour ad lib session

Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigaretteOther: Wintergreen (fleece A), 12 mg nicotineOther: Wintergreen (fleece A), 9 mg nicotineOther: Wintergreen (fleece B), 9 mg NicotineOther: Watermelon Mint (fleece A), 9 mg NicotineOther: UB moist snuff (UB MST), either loose or portioned (pouched).

Interventions

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

Product usage order ASDECBProduct usage order BAESDCProduct usage order CBSAEDProduct usage order DCABSEProduct usage order EDBCASProduct usage order SECDBA

Wintergreen (fleece A), 12 mg nicotine

Product usage order ASDECBProduct usage order BAESDCProduct usage order CBSAEDProduct usage order DCABSEProduct usage order EDBCASProduct usage order SECDBA

Wintergreen (fleece A), 9 mg nicotine

Product usage order ASDECBProduct usage order BAESDCProduct usage order CBSAEDProduct usage order DCABSEProduct usage order EDBCASProduct usage order SECDBA

Wintergreen (fleece B), 9 mg Nicotine

Product usage order ASDECBProduct usage order BAESDCProduct usage order CBSAEDProduct usage order DCABSEProduct usage order EDBCASProduct usage order SECDBA

Watermelon Mint (fleece A), 9 mg Nicotine

Product usage order ASDECBProduct usage order BAESDCProduct usage order CBSAEDProduct usage order DCABSEProduct usage order EDBCASProduct usage order SECDBA

UB moist snuff (UB MST), either loose or portioned (pouched).

Product usage order ASDECBProduct usage order BAESDCProduct usage order CBSAEDProduct usage order DCABSEProduct usage order EDBCASProduct usage order SECDBA

Eligibility Criteria

Age21 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (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 and who also use MST. Participant's usual brand MST product needs to be a moist snuff tobacco product and not a Snus oral tobacco product.
  • 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 (occurring 30 days prior to Screening), or clinical study participation (occurring 30 days prior to Screening) will be allowed at the discretion of an investigator.
  • 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.
  • Reports daily use of MST products and agrees to use the same UB MST throughout the study period. The UB moist snuff is defined as the reported moist snuff brand and style currently used most frequently by the participant.
  • Expired breath carbon monoxide (eCO) level is ≥ 10 ppm and ≤ 100 ppm at Screening and at check-in (Day 1).
  • 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) OR response at Screening to "How soon after you wake up do you place your first dip?" is either "Within 5 minutes" or "6-30 minutes" from the Fagerström Test for Nicotine Dependance-Smokeless Tobacco (FTND-ST) (Ebbert et al., 2006).
  • Positive urine cotinine test (i.e., ≥200 ng/mL) at Screening and at Check-in Day 1.
  • Willing to use Study IPs, their UB cigarette and UB moist snuff (Product S) during the study period.
  • Willing to abstain from tobacco and nicotine use for at least 12 hours prior to the start of each of six 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;
  • +6 more criteria

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 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.
  • 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®), GLP-1 agonists (e.g., Wegovy®, Mounjaro®, and Ozempic®), or lobelia extract within 30 days prior to signing the informed consent form.
  • 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.
  • Any use of daily aspirin (≥ 325 mg) or any use of other anticoagulants.
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

SmokingTobacco UseTobacco Smoking

Interventions

MentholNicotine

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

CyclohexanolsHexanolsFatty AlcoholsAlcoholsOrganic ChemicalsCyclohexane MonoterpenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsMonoterpenesTerpenesLipidsSolanaceous AlkaloidsAlkaloidsHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Brian Keyser

    Reynolds American

    STUDY DIRECTOR

Central Study Contacts

John Darnell

CONTACT

Kristen Prevette

CONTACT

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

June 29, 2026

First Posted

July 6, 2026

Study Start

July 15, 2026

Primary Completion (Estimated)

September 15, 2026

Study Completion (Estimated)

January 31, 2027

Last Updated

July 6, 2026

Record last verified: 2026-06

Data Sharing

IPD Sharing
Will not share