SmokingNCT07685795
Abuse Liability of Four Modern Oral Nicotine Products
A study testing Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette, Wintergreen (fleece A), 12 mg nicotine and Wintergreen (fleece A), 9 mg nicotine in people with Smoking and Smoking Behaviors, run by RAI Services Company.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Smoking, Smoking Behaviors, Tobacco Use
- What is being tested?
- Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette, Wintergreen (fleece A), 12 mg nicotine and Wintergreen (fleece A), 9 mg nicotine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 15 Jul 2026to 31 Jan 2027
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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;
- abstinence;
- non-hormone releasing intrauterine devices (IUD);
- vasectomized partner; or
- post-menopausal and not on hormone replacement therapy.
- Agrees to an in-clinic confinement of seven days (six nights).
- BMI within 18.0 to 40.0 kg/m2, inclusive (minimum weight of at least 50.0 kg at Screening)
Who cannot join
- 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.
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- 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.
- 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.
- 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.
- Individuals ≥ 35 years of age currently using systemic, testosterone, estrogen-containing contraception or hormone replacement therapy.
- 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.
- Plasma donation within (≤) 7 days prior to signing the informed consent and between Screening and check-in Day 1.
- Employed by a tobacco or nicotine company, the study site, or handles raw, unpackaged tobacco- or nicotine-containing products as part of their job.
- 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.
- Drinks more than 21 servings of alcoholic beverages per week.
- Determined by an investigator to be inappropriate for this study.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: An In-Clinic Confinement Study to Assess Elements of Abuse Liability of Four Modern Oral Nicotine Products
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.
Read the detailed description
Smokers who only use filtered menthol or non-menthol cigarettes and who also use loose or pouched moist snuff smokeless tobacco [Moist Snuff Tobacco (MST)] will be recruited into this AL study to evaluate elements of AL of four modern oral (MO) nicotine products (hereinafter, Study IPs) compared to combustible cigarettes (CC) and MST.
For this study, participant's usual brand smokeless tobacco product needs to be moist snuff (loose or pouched) and not a Snus smokeless oral tobacco product.
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 Day 1, participants will check-in at the clinical site to confirm eligibility. Eligible participants will be enrolled, randomized and confined in the clinic for 7 days (6 nights).
Participants will be randomized to a product use sequence (using a Williams Design) in which they will evaluate one IP in each of six separate daily Test Sessions, such that each participant will evaluate a total of six IPs; Wintergreen 12 mg nicotine (fleece A), Wintergreen 9 mg nicotine (fleece A),Wintergreen 9 mg (fleece B), Watermelon Mint 9 mg nicotine (fleece A), participant's usual brand moist snuff tobacco [UB MST], and a high-AL comparator (participant's usual brand cigarette [UB CC]).
On Day 2 and continuing through Day 7, participants will participate in daily Test Sessions that will last approximately 8 hours, consisting of a 1-hour controlled first use period immediately followed by a 7-hour ad libitum period. 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. During each test session, used IP will be collected, and either disposed of (UB CC and loose UB MST) or stored (modern oral IP and pouched UB MST) at -20°C, and shipped to a laboratory of the Sponsor's choosing. For participants whose UB MST is loose MST, a fresh unopened tin/can will be weighed immediately prior to the 'first use' portion of the session before the participant self-selects the amount of loose MST for their initial IP use. The lid will be replaced on the can/tin and weighed to the nearest 0.01g.
Immediately following the 1-hour 'first use' portion of the test session, a 7-hour ad libitum use period will commence. Both types of PD (subjective and physiological) and PK measures will be measured during the 7-hour ad libitum use period. The number, time, and duration of use of IPs that participants request will be recorded; every used IPs (MO and pouched UB MST IPs only) will be collected, stored at -20°C, and shipped to a laboratory of the sponsor's choosing. For participants whose test session IP is loose UB MST, a fresh unopened tin/can or the tin/can used for the initial 1-hour 'first use' session will be weighed immediately prior to the participant self-selects the amount of loose UB MST for their ad libitum test session, then the lid will be replaced to the can/tin and weighed to the nearest 0.01g. After the participant's completion of the 7-hour ad libitum test session, the tin/can of UB MST will be weighed to the nearest 0.01g to determine the total amount of UB MST used during the 7-hour and the entire 8-hour test sessions.
During the remaining ~4 hours of the day following each 8-hour Test Session, a Product Acclimation Period will allow participants ad libitum use of the subsequent day's Test Session assigned MO IP (at least two trial uses; minimum acclimation use requirement), followed by use of their UB CC and UB MST ad libitum, until the 12-hour tobacco and nicotine abstinence period begins. If the participant's UB CC or UB MST are assigned per randomized sequence for use in the next day's Test Session, no (MO) product acclimation is required and participants can use their UB CC and UB MST ad libitum, until the 12-hour tobacco and nicotine abstinence period begins. Used IP (only MO IPs and pouched UB MST) from each of the MO Product Acclimation and/or end of day ad libitum use periods will be collected immediately after use, 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 experiences/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 study and for any follow-up needs after study discharge.
- Conditions
- Smoking, Smoking Behaviors, Tobacco Use, Tobacco Smoking
- Being tested
- Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette, Wintergreen (fleece A), 12 mg nicotine, Wintergreen (fleece A), 9 mg nicotine, Wintergreen (fleece B), 9 mg Nicotine, Watermelon Mint (fleece A), 9 mg Nicotine
- Medical subject headings
- Smoking, Tobacco Use, Tobacco Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Usual Brand (UB) filtered, menthol or non-menthol combustible cigaretteOther
Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette
Wintergreen (fleece A), 12 mg nicotineOther
Wintergreen (fleece A), 12 mg nicotine
Wintergreen (fleece A), 9 mg nicotineOther
Wintergreen (fleece A), 9 mg nicotine
Wintergreen (fleece B), 9 mg NicotineOther
Wintergreen (fleece B), 9 mg Nicotine
Watermelon Mint (fleece A), 9 mg NicotineOther
Watermelon Mint (fleece A), 9 mg Nicotine
UB moist snuff (UB MST), either loose or portioned (pouched).Other
UB moist snuff (UB MST), either loose or portioned (pouched).
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette; Other: Wintergreen (fleece A), 12 mg nicotine; Other: Wintergreen (fleece A), 9 mg nicotine; Other: Wintergreen (fleece B), 9 mg Nicotine; Other: Watermelon Mint (fleece A), 9 mg Nicotine; Other: 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 Receives: Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette; Other: Wintergreen (fleece A), 12 mg nicotine; Other: Wintergreen (fleece A), 9 mg nicotine; Other: Wintergreen (fleece B), 9 mg Nicotine; Other: Watermelon Mint (fleece A), 9 mg Nicotine; Other: 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 Receives: Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette; Other: Wintergreen (fleece A), 12 mg nicotine; Other: Wintergreen (fleece A), 9 mg nicotine; Other: Wintergreen (fleece B), 9 mg Nicotine; Other: Watermelon Mint (fleece A), 9 mg Nicotine; Other: 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 Receives: Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette; Other: Wintergreen (fleece A), 12 mg nicotine; Other: Wintergreen (fleece A), 9 mg nicotine; Other: Wintergreen (fleece B), 9 mg Nicotine; Other: Watermelon Mint (fleece A), 9 mg Nicotine; Other: 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 Receives: Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette; Other: Wintergreen (fleece A), 12 mg nicotine; Other: Wintergreen (fleece A), 9 mg nicotine; Other: Wintergreen (fleece B), 9 mg Nicotine; Other: Watermelon Mint (fleece A), 9 mg Nicotine; Other: 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 Receives: Other: Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette; Other: Wintergreen (fleece A), 12 mg nicotine; Other: Wintergreen (fleece A), 9 mg nicotine; Other: Wintergreen (fleece B), 9 mg Nicotine; Other: Watermelon Mint (fleece A), 9 mg Nicotine; Other: UB moist snuff (UB MST), either loose or portioned (pouched). |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUECPL 5-60
area under the effect curve (AUEC) for PL (VAS score-versus-time)
Measured: 5 minutes to 60 minutes
Emax PL
maximum effect (maximum PL VAS score after the start of IP use)
Measured: 60 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2026
- Study start15 Jul 2026 (estimated)
- Primary completion15 Sep 2026 (estimated)
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SmokingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RAI Services Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Brian Keyser, Study director, Reynolds American
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07685795
- Sponsor's protocol ID
- IHI262101
- Status last verified
- Jun 2026
- First submitted
- 29 Jun 2026
- Last updated
- 6 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No