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Not yet recruitingNCT07881848Updated Oct 20, 2026

A Study to Assess Nicotine Uptake From a Menthol Electronic Nicotine Delivery System Product

An interventional study of Menthol 5% and Combustible cigarette in Smoking Behaviors, Smoking ( Cigarette) and Tobacco Use, sponsored by RAI Services Company. Not yet recruiting. Open to participants aged 21 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-20.

Sponsored by RAI Services Company (part of British American Tobacco) · Not applicable, Interventional, and Other

Updated Oct 20, 2026Newly registeredGo to Updates ↓
Phase
Not applicable
Study type
Interventional
Enrollment
28
Allocation
Randomized
Ages
21 Years to 60 Years
Sex
All
01

Study summary

This will be a randomized, open-label, 2-way crossover, single-site study designed to evaluate elements of abuse liability (AL), including subjective effects and physiological measures (pharmacodynamics [PD]), and plasma nicotine uptake (pharmacokinetics [PK]) of Menthol ENDS investigational product (IP) relative to each participant's usual brand (UB) menthol cigarette. The study will be conducted in a confinement setting in generally healthy adult menthol cigarette smokers and dual users of menthol cigarettes and ENDS products.

Read the detailed description

Current adult menthol cigarette smokers and dual users of menthol cigarettes and ENDS will be recruited into this study to evaluate elements of AL of the Menthol ENDS, in comparison to participant's usual brand (UB) cigarette. The study design, including daily product use and test session schedule, is illustrated in Figure 1-1. A summary of study activities is provided below:

Potential participants will undergo a pre-screening interview followed by a Screening Visit within 28 days prior to enrollment, randomization, and study confinement to assess eligibility.

Eligible participants will be scheduled for a check-in and randomization visit. At this visit, eligibility will be reconfirmed prior to randomization to a product use sequence, based on a Williams design. Participants will then enter a 4-day, 3 night confinement period at the clinical site.

On study Day -1, participants will enter a product familiarization period during which they will be required to use the Menthol ENDS (Product B [Menthol 5%]) at least once. Use of the Menthol ENDS during the familiarization period will be approximately 5 minutes. After completing this familiarization, participants will be permitted to smoke their UB cigarettes ad libitum. Participants who also use other tobacco and/or nicotine-containing products such as ENDS, smokeless tobacco or modern oral nicotine products in addition to their UB cigarettes will not have access to those products during the study.

Following the product familiarization period, participants will enter a product acclimation period beginning on Day 1 and each day prior to a test session. During each daily product acclimation period, participants will be required to use their randomized Menthol ENDS assigned for use in the subsequent day's test session (no product acclimation for UB cigarette) at least four times. For the Menthol ENDS, product use period during the daily acclimation period will last approximately 5 minutes. After completing this requirement, participants will be permitted to smoke their UB cigarettes ad libitum. Pharmacy logs will be used to capture information on product usage during the product familiarization and acclimation periods.

At the end of the product acclimation period and ad libitum use of the participant's UB cigarette, participants will abstain from use of all tobacco- and nicotine-containing products for a minimum of 12 hours prior to each test session, occurring on the following day. In addition, participants will be required to abstain from any caffeine-containing products for 4 hours prior to the start of each test session through the end of the test session.

Starting on Day 2 and continuing through Day 3, each participant will participate in two consecutive daily test sessions, evaluating one study product per session. Over the course of the study, each participant will evaluate a total of two products: one Menthol ENDS and a high-AL comparator (the participant's UB cigarette).

During each test session, subjective effects questionnaire responses will be collected before, during, and after each product use. Blood samples will then be collected for plasma nicotine PK assessments, and, subsequently, the collection of physiological measures after the assigned product use.

The active period of each test session will start with the assigned product use initiation and last approximately 4 hours during and following product use. During each test session, participants will smoke one UB menthol cigarette or use the Menthol ENDS ad libitum for approximately 5 minutes, based on the product use sequence to which participants will be randomized.

Participants' use of the Menthol ENDS will be self-defined during the 5-minute ad libitum IP use session; specific parameters around puff duration, volume, inter- puff interval, and quantity will not be prescribed.

Participant general health and well-being will be monitored throughout the study by the Principal Investigator (PI) or qualified designee by adverse events (AEs) assessments, vital sign measurements, physical examinations (including an oral examination), and clinical laboratory tests. The Medical Monitor will be available for consultation throughout the study and for any necessary follow-up after discharge.

02

Conditions studied

  • Smoking Behaviors
  • Smoking ( Cigarette)
  • Tobacco Use
  • Abuse Liability
03

In context

Smoking

325 studies on the registry are indexed under Smoking; 141 are open to participants now.

This study's planned enrollment of 28 is below the median of 117 across 250 interventional studies indexed under Smoking.

Browse Smoking studies →

Lead sponsor

RAI Services Company is the lead sponsor of 53 studies on the registry; 12 are open to participants now.

First submitted after RAI Services Company became part of British American Tobacco.

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

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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 male or female, 21 to 60 years of age, inclusive, at the time of consent.
  3. Expired breath carbon monoxide level is ≥ 10 ppm and ≤ 100 ppm at Screening.
  4. Positive urine cotinine test at Screening.
  5. Smokes combustible filtered, menthol cigarettes, 83 mm to 100 mm in length.
  6. Agrees to smoke same menthol UB cigarette throughout the study period. UB cigarette is defined as the cigarette brand style currently smoked most frequently by the participant.
  7. Participants must meet one (a or b) of the following tobacco use conditions:

    a. Sole smoker of filtered menthol cigarettes who self reports: i. Smoking at least 10 cigarettes per day (on average) and inhales the smoke, for at least 6 months prior to Screening. Brief periods of abstinence due to illness, quit attempt (more than 30 days prior to Screening), or clinical study participation (more than 30 days prior to Screening) will be allowed at the discretion of an investigator b. Dual user of cigarettes and ENDS who self-reports: i. Smoking at least 10 cigarettes per day (on average) and inhales the smoke, for at least 6 months prior to Screening Visit. Brief periods of abstinence more than 30 days prior to screening due to illness, quit attempt or clinical study participation will be allowed at the discretion of an investigator, and ii. Using a nicotine-containing ENDS (cartridge or a tank system). NOTE: Cigarette smokers or ENDS users who also use other tobacco- or nicotine-containing products (e.g., smokeless tobacco, and modern oral nicotine products) on no more than one day per week will not be excluded from study participation.

  8. 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."
  9. Willing to use only menthol UB cigarettes and the Menthol ENDS during the study period.
  10. Willing to abstain from tobacco and nicotine use for at least 12 hours prior to each test session.
  11. Females must be willing to use a form of contraception acceptable to an investigator from the time of signing informed consent until End-of-Study. Examples of acceptable means of birth control include, but are 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 (IUDs) or hormone-releasing IUDs (e.g., Mirena or Kyleena);
    4. Vasectomized partner;
    5. Post-menopausal and not on hormone replacement therapy; or
    6. Sexual abstinence, defined as refraining from intercourse, when this is in line with the preferred and usual lifestyle of the participant.
  12. Males must use an acceptable method of birth control from Day -1 "check-in" until the end of the study, unless they have had a vasectomy or are abstinent from heterosexual intercourse, or their female partner is not able to bear children.
  13. Agrees to in-clinic confinement of 4 days and 3 nights.

Exclusion criteria

Exclusion Criteria:

  1. 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.
  2. History, presence of, or clinical laboratory test results indicating diabetes.
  3. Systolic blood pressure of > 160 mmHg or a diastolic blood pressure of > 95 mmHg, measured after being seated for five minutes at Screening and at check-in Day -1.
  4. Weight of ≤ 110 pounds (≤ 50.0 kg) at Screening.
  5. Hemoglobin level is \< 12.5 g/dL for females or \<13.0 g/dL for males at Screening.
  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's discretion.
  7. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
  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. Must not be a current regular user (i.e., > 5 times per month) of any tobacco products other than menthol cigarettes or ENDS within the last 6 months prior to screening.
  10. 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 the signing of informed consent.
  11. History or presence of bleeding or clotting disorders.
  12. Use of daily aspirin (≥ 325 mg) or other daily anticoagulants.
  13. Whole blood donation within 8 weeks (≤ 56 days) prior to the signing of informed consent and between Screening and check-in Day -1.

    NOTE: Participants will be advised against scheduling a whole blood donation for at least 7 days following study completion.

  14. Plasma donation within ≤ 7 days prior to the signing of informed consent and between Screening and check-in Day -1.

    NOTE: Participants will be advised against scheduling a plasma donation for at least 7 days following study completion.

  15. Participation in another clinical trial within ≤ 30 days prior to the signing of informed consent. The 30-day window for each participant will be derived from the date of the last study event in the previous study to the time of signing the ICF in the current study.
  16. Females who have a positive pregnancy test at Screening or check-in on Day -1, are pregnant, breastfeeding, or intend to become pregnant during the course of the study.
  17. Individuals ≥ 35 years of age currently using systemic, estrogen-containing contraception or hormone replacement therapy.
  18. A positive drug screen or alcohol test (urine or breath) at Screening or at check-in (Day -1), with the exception of positive results for tetrahydrocannabinol (THC). If positive for THC at check-in, a cannabis intoxication evaluation will be performed, and inclusion will be at the discretion of an investigator.
  19. Postpones a decision to quit using tobacco- or nicotine-containing products in order to participate in this study or a previous quit attempt within ≤ 30 days prior to the signing of the ICF.
  20. Has a significant history of alcoholism or drug abuse within 24 months prior to Screening, as determined by an investigator, or has a positive alcohol test at Screening or check-in on Day -1.
  21. Employed by a tobacco or nicotine company, the study site, or handles tobacco- or nicotine-containing products as part of their job.
  22. Individuals or their family members that have ongoing litigation with tobacco company(ies).
  23. 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
28 participants (estimated)

Study arms

  • Experimental
    Product usage order AB

    Subjects will use each of the 2 products during an evaluation period, followed by a 4 hour Test Session.

    Other: Menthol 5% · Other: Combustible cigarette

  • Experimental
    Product usage order BA

    Subjects will use each of the 2 products during an evaluation period, followed by a 4 hour Test Session.

    Other: Menthol 5% · Other: Combustible cigarette

Interventions

  • OtherMenthol 5%

    Menthol ENDS 5%

  • OtherCombustible cigarette

    Usual brand filtered menthol combustible cigarette

06

What researchers measure

Primary outcomes

  1. AUC nic 3-240

    Baseline-adjusted area under the plasma nicotine concentration-versus-time curve from time 3 to 240 minutes after the start of IP use

    Time frame: 3 minutes to 240 minutes

  2. Emax PL

    maximum PL VAS score after the start of IP use

    Time frame: 240 minutes

07

Study locations

No study locations are listed for this record.

08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Timeline

1 registry update since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Start is estimated for Nov 2026; primary completion for Dec 2026, 1 month later.

Of 155 interventional studies with no phase under Smoking, half reached primary completion within 37 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 59. This study's planned 1 month is below that.

How these figures are worked out, and which studies are left out of them.

Registered
Oct 13, 2026
First posted
Oct 20, 2026
StartEst.
Nov 15, 2026
Primary completionEst.
Dec 2026
CompletionEst.
Jul 2027
Last update
Oct 20, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Registered
First appeared on the registry. No changes since
Oct 20, 2026
Show all 1 update
  1. Oct 20, 2026
    First appeared on the registry

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07881848
Responsible party
Sponsor
First posted
Oct 20, 2026
Start date
Nov 15, 2026 (estimated)
Primary completion
Dec 2026 (estimated)
Completion
Jul 2027 (estimated)
Last update
Oct 20, 2026

Study contacts

Emily Smith
Contact
smithe13@rjrt.com
3367412396
Kristen Prevette
Contact
prevetk1@rjrt.com
3364143176
Milly Kanobe
study director · Reynolds American

Oversight

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

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