SmokingNCT07132814
Abuse Liability for Five Modern Oral Nicotine Products
A study testing Product A, Product B and Product C in people with Smoking and Smoking Behaviors, run by RAI Services Company at 1 site in United States.
Trial summary
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… 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?
- Product A, Product B and Product C
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2025to 31 Aug 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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.
- 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.
- 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.
- 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.
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- Expired breath carbon monoxide (ECO) level is ≥ 10 ppm and ≤ 100 ppm at Screening.
- Positive urine cotinine test (e.g., >200 ng/mL) via dipstick at Screening.
- 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" .
- Willing to use the UB cigarette, Study IPs, and Nicorette® nicotine gum (Arm 2 only) during the study period.
- Willing to abstain from tobacco and nicotine use for at least 12 hours prior to the start of each of four 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;
- non-hormone releasing intrauterine devices (IUD) or hormone-releasing IUDs (e.g., Mirena or Kyleena);
- vasectomized partner; or
- post-menopausal and not on hormone replacement therapy.
- Agrees to an in-clinic confinement of five days (four nights).
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 last 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.
- Weight of ≤ 50.0 kg at screening or at check-in.
- 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®), or lobelia extract within (≤) 30 days prior to signing the informed consent.
- 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
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Dr. Vince Clinical Research
Overland Park, Kansas, 66212
Patricia Deluca, tcdeluca@drvince.com
About this study
Official title: An In-Clinic Confinement Study to Assess Elements of Abuse Liability for Five Modern Oral Nicotine Products
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
Read the detailed description
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
- Smoking, Smoking Behaviors, Tobacco Use, Tobacco Smoking
- Being tested
- Product A, Product B, Product C, Product D, Product E
- 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.
Product AOther
Usual Brand (UB) filtered, non-menthol or menthol combustible cigarette
Product BOther
8 mg nicotine oral product
Product COther
12 mg nicotine oral product
Product DOther
6 mg nicotine oral product
Product EOther
8 mg nicotine oral product
Product FOther
8 mg nicotine oral product
Product NOther
Nicorette® White Ice Mint 4 mg nicotine polacrilex gum
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | 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. Receives: Other: Product A; Other: Product B; Other: Product C; Other: Product D |
| Arm 2 | Experimental | 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. Receives: Other: Product A; Other: Product E; Other: Product F; Other: Product N |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUECPL 5-240
area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use
area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use
area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use
area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use.
Measured: 5 minutes to 240 minutes
Emax PL
maximum effect (maximum PL VAS score after the start of IP use)
Measured: 240 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2025
- Study start15 Dec 2025
- Primary completion15 Apr 2026 (estimated)
- Study completion31 Aug 2026 (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.
- More trials run by RAI Services CompanyThe sponsor's other registered studies.
- 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
- 40 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
- NCT07132814
- Sponsor's protocol ID
- CSD252401
- Status last verified
- Dec 2025
- First submitted
- 13 Aug 2025
- Last updated
- 30 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An In-Clinic Confinement Study to Assess Elements of Abuse Liability for Five Modern Oral Nicotine Products
- ClinicalTrials.gov ID
- NCT07132814
- Acronym / sponsor ID
- CSD252401
- Conditions
- Smoking, Smoking Behaviors, Tobacco Use, Tobacco Smoking
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- RAI Services CompanyIndustry (pharma, biotech, devices)
- Study start
- 15 Dec 2025 (actual)
- Primary completion
- 15 Apr 2026 (estimated)
- Study completion
- 31 Aug 2026 (estimated)
- First posted
- 20 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Other: Product A, Other: Product B, Other: Product C, Other: Product DEnrolled 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. |
| Arm 2 | Experimental | Other: Product A, Other: Product E, Other: Product F, Other: Product NEnrolled 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. |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- 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.
- 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.
- 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.
Key exclusion criteria (24 listed)
- 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 last 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Product AUsual Brand (UB) filtered, non-menthol or menthol combustible cigarette | Other | Arm 1, Arm 2 |
| Product B8 mg nicotine oral product | Other | Arm 1 |
| Product C12 mg nicotine oral product | Other | Arm 1 |
| Product D6 mg nicotine oral product | Other | Arm 1 |
| Product E8 mg nicotine oral product | Other | Arm 2 |
| Product F8 mg nicotine oral product | Other | Arm 2 |
| Product NNicorette® White Ice Mint 4 mg nicotine polacrilex gum | Other | Arm 2 |
Primary outcome
AUECPL 5-240
Time frame: 5 minutes to 240 minutes
area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use.
Emax PL
Time frame: 240 minutes
maximum effect (maximum PL VAS score after the start of IP use)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Brian Keyser study director
Reynolds American
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Product A, Product B and Product C in people with Smoking and Smoking Behaviors, run by RAI Services Company at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact John Darnell (3367410386, darnelj2@rjrt.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUECPL 5-240 (time frame: 5 minutes to 240 minutes). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2025.