Tobacco UseNCT06356610
Pharmacokinetic and Subjective Effects of Heated Tobacco Products
A study testing Product A, Product B and Product C in people with Tobacco Use, run by Altria Client Services LLC at 3 sites in United States.
Trial summary
This is a randomized, controlled, six-way crossover clinical study to characterize the nicotine PK (pharmacokinetic) and subjective effects of HTPs (Heated Tobacco Products) comprised of 2 menthol varieties and 2 tobacco flavor varieties (Ploom® HTPs, Japan Tobacco Inc.) in adult menthol and non-menthol combustible… Read more about this study
- Who is it for?
- Ages 22 to 65 years
- Conditions the study is for
- Tobacco Use
- What is being tested?
- Product A, Product B and Product C
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 3 sitesUnited States
- Study dates
- 6 Feb 2024to 18 Dec 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 22 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must be informed of the nature and risks of the study and voluntarily give written informed consent prior to screening.
- Healthy adult males and females ≥ 22 and ≤ 65 years of age, inclusive, at screening.
- Participants must self-report currently smoking menthol or non-menthol factory manufactured combustible cigarettes. Participants will have a history of smoking ≥ 10 to
- ≤ 30 menthol or non-menthol factory manufactured combustible cigarettes daily for at least 12 months prior to screening. Prior to screening, brief periods (i.e., up to 7 consecutive days) of non-smoking within 90 days before Check-in (e.g., due to illness or participation in a clinical study where tobacco use was prohibited) will not be exclusionary at the discretion of the Investigator (other non-daily tobacco use, except for heated tobacco use, within 30 days prior to screening are not exclusionary).
- Participants must be generally healthy, free of lifetime malignant tumors, and without clinically significant abnormalities as assessed by the Investigator based on the review of medical and surgical history, physical examination, vital signs, 12-lead ECG, and laboratory evaluations conducted at screening and Check-in, as applicable (refer to Table 1). A single repeat measurement/test may be performed to confirm vital signs, 12-lead ECG, and clinical laboratory tests abnormalities (i.e., to confirm that a participant is eligible).
- Screening and Check-in systolic/diastolic blood pressure ≤ 150/90 mmHg measured after being seated quietly for at least 10 minutes. Two rechecks may be performed at the Investigator's discretion.
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- Urine cotinine ≥ 500 ng/mL at screening.
- Exhaled carbon monoxide ≥ 10 ppm at screening.
- Negative pregnancy test at screening and Check-in (Day -1) for all female participants.
- Female participants who are sexually active and of childbearing potential (i.e., not surgically sterile at least 6 months prior to Check-in nor post-menopausal with amenorrhea for at least 1 year prior to Check-in and FSH levels consistent with postmenopausal status) must not be lactating and must have been using one of the following forms of contraception from 3 months before first study product administration through 30 days after the final administration of study product:
- hormonal (e.g., oral, vaginal ring, transdermal patch, implant, injection) consistently for at least 3 months prior to Check-in, when used in combination with male condoms with spermicide (use of NuvaRing® is at the Investigator's discretion)
- double barrier (e.g., condom with spermicide or diaphragm with spermicide) consistently for at least 2 weeks prior to Check-in
- intrauterine device or system (utilize Investigator discretion regarding use of hormonal or nonhormonal devices) for at least 3 months prior to Check-in
- exclusive partner who is clinically sterile (i.e., documented infertility or surgical sterilization; see below for additional information on sterility) or has been vasectomized for at least 6 months (inclusive) prior to Check-in Note: Sexual abstinence, defined as refraining from intercourse, is allowed when this is in line with the preferred and usual lifestyle of the participant. Female participants of childbearing potential who are not currently engaging in heterosexual intercourse must agree to use one of the above methods of birth control through completion of study, in the event that they have heterosexual intercourse during the course of the study.
- Female participants who are of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to Check-in:
- hysteroscopic sterilization with documentation of success with hysterosalpingogram
- bilateral tubal ligation or bilateral salpingectomy
- hysterectomy
- bilateral oophorectomy
- Essure® or be post-menopausal with amenorrhea for at least 1 year prior to Check-in and confirmed by FSH levels consistent with post-menopausal status.
- Able to communicate effectively with the study personnel and willing to comply with the requirements of the study.
- Willing and able to use all of the study products. This includes product use during the at-home product trial and the in-confinement product use sessions. If participants are unwilling to use or unable to tolerate any of the study products they will not participate in this study.
Who cannot join
- Use of any HTPs within the past 30 days prior to the screening visit; occasional use (i.e., not daily use) of other types of tobacco- or nicotine-containing products other than factory manufactured combustible cigarettes (e.g., roll-your-own cigarettes, e-cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) are allowed within the past 30 days prior to screening.
- Any postponement of a quit attempt to participate in the study; or any attempts to quit smoking in the 3 months prior to Day -1 (Check-in).
- Self-reported puffers (i.e., smokers who draw smoke from the combustible cigarette into the mouth and throat but do not inhale).
- Poor dentition that prevents participant from using nicotine gum.
- History or presence of any type of malignant tumor or clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other condition that, in the opinion of the Investigator, would interfere with the absorption, distribution, metabolism, or excretion of cotinine or jeopardize the safety of the participant or impact the validity of the study results.
- Current evidence or any history of congestive heart failure.
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- Any other condition or prior therapy that, in the Investigator's opinion, would make the participant unsuitable for the study, or unable or unwilling to comply with the study procedures.
- Clinically significant abnormal vital sign, physical examination (including oral cavity an oropharynx), medical history, or clinical laboratory finding(s), in the opinion of the Investigator.
- Positive test for human immunodeficiency virus (HIV)-1 or HIV-2; or hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) consistent with current infection at screening.
- Diabetes mellitus that is not controlled by diet/exercise alone, in the opinion of the Investigator. Fasting plasma glucose > 126 mg/dL (7 mmol/L) is exclusionary. One recheck may be performed for fasting plasma glucose values > 126 mg/dL but < 200 mg/dL.
- An acute illness (e.g., upper respiratory infection, viral infection) requiring treatment with prescribed medicines within 2 weeks prior to Check-in.
- History of surgery or major trauma within 12 weeks of screening, or surgery planned during the study through EOS.
- History of alcohol abuse or drug abuse within 24 months prior to Check-in.
- Consumption of alcohol-containing food or beverages within 48 hours prior to Check-in.
- Positive screen for alcohol (breath or urine) or any of the following drugs of abuse (urine), regardless of the reason of use: amphetamines, methamphetamines, opiates, cannabinoids, or cocaine at screening or Check-in.
- Fever (i.e., body temperature > 100.5°F) at screening or Check-in; 1 recheck may be performed at the Investigator's discretion.
- Body mass index (NHLBI) > 40.0 kg/m2 or < 18.0 kg/m2 at screening.
- Estimated glomerular filtration rate < 80 mL/minute using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (Medscape) at screening.
- Serum alanine aminotransferase ≥ 1.5 times the upper limit of normal and/or aspartate aminotransferase ≥ 2.0 times the upper limit of normal at screening; 1 recheck may be performed at the Investigator's discretion.
- Female participants who are pregnant (positive pregnancy test at screening or Check-in), lactating, or intend to become pregnant from screening through EOS.
- Use of prescription or over-the-counter (OTC) bronchodilator medication (e.g., inhaled or oral β-agonists) for treatment of any illness within 12 months prior to Check-in.
- Use of antibiotics within 2 weeks prior to Check-in. Also refer to Section 5.7.1.
- Use of medications known or are suspected to interact with cytochrome P450 2A6 (including, but not limited to, amiodarone, amlodipine, amobarbital, buprenorphine, clofibrate, clotrimazole, desipramine, disulfiram, entacapone, fenofibrate, isoniazid, ketoconazole, letrozole, methimazole, methoxsalen, metyrapone, miconazole, modafinil, orphenadrine, pentobarbital, phenobarbital, pilocarpine, primidone, propoxyphene, quinidine, rifampicin, rifampin, secobarbital, selegiline, sulconazole, tioconazole, tranylcypromine) within 14 days or 5 half-lives of the drug, whichever is longer, prior to Check-in.
- Has taken other investigational drugs/products or participated in any clinical study for an investigational drug, device, biologic, or for a tobacco product within 30 days or 5 halflives (if known) of the investigational product's PK, pharmacodynamic, or biological activity (if known), whichever is longer, prior to first administration of study product in this study or is currently participating in another clinical study; or participation in > 2 ALCS-sponsored studies within the past 12 month period prior to Check-in.
- Has received a vaccination within 14 days prior to Check-in.
- Plasma donation within 7 days prior to Day 1.
- Donation of ≥ 1 unit of blood or blood products (with the exception of plasma as noted), had significant blood loss > 450 mL, or received whole blood or a blood product transfusion within 56 days prior to Day -1.
- Strenuous activity (as assessed by the Investigator) within 48 hours prior to Check-in.
- Participant or a first-degree relative (i.e., parent, sibling, child, spouse) is a current or former employee of the tobacco industry or a named party or class representative in litigation with any tobacco company.
- Participant or a first-degree relative (i.e., parent, sibling, child, spouse) is a current employee of the study site.
- Unwilling or unlikely to comply with the requirements of the study.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Alliance for Multispecialty Research, LLC
Knoxville, Tennessee, 37920
Alliance for Multispecialty Research, LLC
Lexington, Kentucky, 40509
QPS Bio-Kinetic
Springfield, Missouri, 65802
About this study
Official title: A Randomized, Controlled, Six-way Crossover Clinical Study To Characterize The Nicotine Pharmacokinetics And Subjective Effects Of Four Heated Tobacco Products In Adult Menthol And Nonmenthol Cigarette Smokers
This is a randomized, controlled, six-way crossover clinical study to characterize the nicotine PK (pharmacokinetic) and subjective effects of HTPs (Heated Tobacco Products) comprised of 2 menthol varieties and 2 tobacco flavor varieties (Ploom® HTPs, Japan Tobacco Inc.) in adult menthol and non-menthol combustible cigarette smokers (males and females between the ages of 22 and 65). The study will include participants' UBCC (Usual Brand Combustible Cigarette) and a nicotine gum (Nicorette®) as high and low abuse liability reference products, respectively, to the HTP. Study participation is expected to last up to 34 days, including a 28-day screening period (that includes a 5-day at-home HTP product trial period), and a 6-day in-clinic confinement period (from Check-in [Day -1] through the end-of-study [EOS] visit on Day 6).
Read the detailed description
This is a randomized, controlled, six-way crossover clinical study to characterize the nicotine PK and subjective effects of HTPs (2 menthol varieties, Products A and B; 2 tobacco flavor varieties, Products C and D) in adult menthol and non-menthol combustible cigarette smokers. The study will include participants' UBCC (Product F) and a nicotine gum (Product E) as high and low abuse liability reference products, respectively, to the HTP.
Product A: Ploom® 3.1 HTP - Menthol HTS; MX3 (681) Product B: Ploom® 3.1 HTP - Menthol HTS; MX5 (706) Product C: Ploom® 3.1 HTP - Tobacco HTS; R8 (120) Product D: Ploom® 3.1 HTP - Tobacco HTS; RX4 (953) Product E: Nicorette® 4 mg Mint Nicotine Gum Product F: Combustible Cigarette (menthol or non-menthol), participant's usual brand
The study will include generally healthy adult males and females who smoke factory manufactured combustible cigarettes. This study will recruit approximately 60 participants (composed of approximately 30 menthol and 30 non-menthol adult smokers) in an attempt to obtain approximately 48 study completed participants (approximately 24 menthol and 24 non-menthol smokers). Adult participants will be between 22 and 65 years of age at screening, inclusive. Participants must have a history of smoking ≥ 10 to ≤ 30 menthol or non-menthol cigarettes daily for at least 12 months prior to screening.
Enrolled participants will be randomized based on sex and their UBCC (menthol or non-menthol) to one of 6 product use sequences.
Screening will occur within 28 days prior to Day 1 and includes administering the FTCD (Fagerstrom Test for Cigarette Dependence), standard safety procedures, collection of baseline information, and a 5-day at-home HTP product trial period.
Enrollment visit (Day -6) will occur 5 days prior to Check-in (Day -1). Participants will receive the Ploom® HTP products for at-home product acclimation to become familiar with the product during the next 5 days. Training on how to use the Ploom® HTP device will be provided to each participant at the Enrollment visit. Participants will receive all four varieties of HTS on Day -6 and begin the at-home product trial. Participants are required to use each HTS variety at least once a day ad libitum for a minimum of 20 HTS uses over 5 days.
Participants will check-in on the morning of Day -1. Product use sequence randomization and assignment will also occur on Day -1. Participants will be randomized based on sex and their UBCC (menthol or non-menthol) to one of six product use sequences. Once participants are randomized to a product use sequence, product use sessions in confinement will start. Participants will remain in confinement at the clinic until completion of all study activities on Day 6.
Starting on Day -1 (following Check-in) through Day 5, depending on the randomized product use sequence, participants will use their assigned product (HTP, UBCC, or nicotine gum) during an afternoon product use session. Participants will use the same assigned product to be tested during the next day's morning ad libitum product use PK test session (e.g., if a participant is assigned to Product A [HTP] as the product to be used in the morning ad libitum product use PK test session on Day 1, the participant will use Product A [HTP] during the afternoon product use session on Day -1). The afternoon product use session should be no more than approximately 6 hours long. Participants will be required to use the assigned study product at least once, but no more than six HTS, UBCC, or nicotine gum ad libitum per daily afternoon product use sessions. Participants will then be required to abstain from any tobacco- or nicotine-containing products for at least 12 hours prior to the start of the following morning's ad libitum product use PK test session. Morning ad libitum product use PK test sessions will occur on the mornings of Days 1, 2, 3, 4, 5, and 6 (for a total of 6 morning ad libitum product use PK test sessions).
During the morning ad libitum product use PK test session, participants will use the assigned study product per their assigned product use sequence. Participants will use a single UBCC or HTP for 5 minutes ad libitum or use the nicotine gum for 30 minutes per product use instruction. Blood samples for PK will be collected prior to and for 3 hours following the start of each morning ad libitum product use PK test session. Heart rate measurements will be taken at specified time points during each morning ad libitum product use PK test session. In addition, participants will complete subjective effects questionnaires (Product Liking, Tobacco/Nicotine Withdrawal, Direct Effects of Product, Use Product Again, and mCEQ) at designated time points during each morning ad libitum product use PK test session. Participants will remain in confinement starting with Check-in on Day -1 until discharge after all study activities are completed on Day 6. Participants will not be forced to use the tobacco/nicotine products at any time during the study.
- Conditions
- Tobacco Use
- Being tested
- Product A, Product B, Product C, Product D, Product E
- Keywords
- Tobacco, Smoking, Heated tobacco
- Medical subject headings
- Tobacco Use, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Product AOther
Also called Ploom® 3.1 HTP - Menthol HTS; MX3 (681)
Use of Product A in controlled use and ad libitum use sessions
Product BOther
Also called Ploom® 3.1 HTP - Menthol HTS; MX5 (706)
Use of Product B in controlled use and ad libitum use sessions
Product COther
Also called Ploom® 3.1 HTP - Tobacco HTS; R8 (120)
Use of Product C in controlled use and ad libitum use sessions
Product DOther
Also called Ploom® 3.1 HTP - Tobacco HTS; RX4 (953)
Use of Product D in controlled use and ad libitum use sessions
Product EOther
Also called Nicorette® 4 mg Mint Nicotine Gum
Use of Product E in controlled use and ad libitum use sessions
Product FOther
Also called Combustible Cigarette (menthol or nonmenthol), participant's usual brand
Use of Product F in controlled use and ad libitum use sessions
| Study group | Role | What they receive |
|---|---|---|
| Randomization Sequence 1: ABFCED | Experimental | Usage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order:
Product A Product B Product F Product C Product E Product D Receives: Other: Product A; Other: Product B; Other: Product C; Other: Product D; Other: Product E; Other: Product F |
| Randomization Sequence 2: BCADFE | Experimental | Usage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order:
Product B Product C Product A Product D Product F Product E Receives: Other: Product A; Other: Product B; Other: Product C; Other: Product D; Other: Product E; Other: Product F |
| Randomization Sequence 3: CDBEAF | Experimental | Usage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order:
Product C Product D Product B Product E Product A Product F Receives: Other: Product A; Other: Product B; Other: Product C; Other: Product D; Other: Product E; Other: Product F |
| Randomization Sequence 4: DECFBA | Experimental | Usage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order:
Product D Product E Product C Product F Product B Product A Receives: Other: Product A; Other: Product B; Other: Product C; Other: Product D; Other: Product E; Other: Product F |
| Randomization Sequence 5: EFDACB | Experimental | Usage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order:
Product E Product F Product D Product A Product C Product B Receives: Other: Product A; Other: Product B; Other: Product C; Other: Product D; Other: Product E; Other: Product F |
| Randomization Sequence 6: FAEBDC | Experimental | Usage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order:
Product F Product A Product E Product B Product D Product C Receives: Other: Product A; Other: Product B; Other: Product C; Other: Product D; Other: Product E; Other: Product F |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline-adjusted Plasma Nicotine Concentration Pharmacokinetic (PK) Parameters [Cmax] Assessment
Characterize PK parameters of nicotine in plasma during and after a single ad libitum use of HTP (two menthol and two tobacco flavor varieties) test products relative to UBCC and the nicotine gum reference products.
Cmax: Maximum measured plasma concentration over the duration of the measurement interval from time zero (defined as the start of product use) to 180 minutes post-use on each Study Day 1 through Day 6.
Measured: from time zero (defined as the start of product use) to 180 minutes post-use on each Day 1 through Day 6
Baseline-adjusted Plasma Nicotine Concentration Pharmacokinetic (PK) Parameter [AUC(0-180)] Assessment
Characterize PK parameters of nicotine in plasma during and after a single ad libitum use of HTP (two menthol and two tobacco flavor varieties) test products relative to UBCC and the nicotine gum reference products.
AUC(0-180): Area under the nicotine concentration-time curve calculated using linear trapezoidal summation from time zero (defined as the start of product use) to 180 minutes post-use on each Study Day 1 through Day 6.
Measured: from time zero (defined as the start of product use) to 180 minutes post-use on each Study Day 1 through Day 6
Baseline-adjusted Plasma Nicotine Concentration Pharmacokinetic (PK) Parameter [Tmax] Assessment
Characterize PK parameters of nicotine in plasma during and after a single ad libitum use of HTP (two menthol and two tobacco flavor varieties) test products relative to UBCC and the nicotine gum reference products.
Tmax: Time of the maximum measured plasma concentration over the duration of the measurement interval.
Measured: Day 1 through Day 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2024
- Study start6 Feb 2024
- Primary completion14 Apr 2024
- Study completion18 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tobacco UseStudies 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
- Model description
- A randomized, controlled, six-way crossover clinical study to characterize the nicotine PK and subjective effects of HTPs (2 menthols, Products A and B; 2 tobacco flavors, Products C and D). Reference products include participants' UBCC (Product F) and nicotine gum (Product E). On Day -1 participants who completed the at-home study product trial and meet all inclusion/ exclusion criteria to be randomized at 1:1:1:1:1:1 ratio into 1 of 6 sequences in a 6x6 Latin Square Design as listed below: Sequence 1 = ABFCED; Sequence 2 = BCADFE; Sequence 3 = CDBEAF; Sequence 4 = DECFBA; Sequence 5 = EFDACB; Sequence 6 = FAEBDC. Product A: Ploom® 3.1 HTP - Menthol HTS; MX3 (681); Product B: Ploom® 3.1 HTP - Menthol HTS; MX5 (706); Product C: Ploom® 3.1 HTP - Tobacco HTS; R8 (120); Product D: Ploom® 3.1 HTP - Tobacco HTS; RX4 (953); Product E: Nicorette® 4 mg Mint Nicotine Gum; Product F: Combustible Cigarette (menthol or non-menthol), participant's usual brand
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Altria Client Services LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Celerion
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06356610
- Sponsor's protocol ID
- ALCS-REG-23-08-HT
- Status last verified
- Nov 2025
- First submitted
- 12 Mar 2024
- Last updated
- 27 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- 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 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled, Six-way Crossover Clinical Study To Characterize The Nicotine Pharmacokinetics And Subjective Effects Of Four Heated Tobacco Products In Adult Menthol And Nonmenthol Cigarette Smokers
- ClinicalTrials.gov ID
- NCT06356610
- Acronym / sponsor ID
- ALCS-REG-23-08-HT
- Conditions
- Tobacco Use
- Keywords
- Tobacco, Smoking, Heated tobacco
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Altria Client Services LLCIndustry (pharma, biotech, devices)
- Collaborators
- Celerion
- Study start
- 6 Feb 2024 (actual)
- Primary completion
- 14 Apr 2024 (actual)
- Study completion
- 18 Dec 2024 (actual)
- First posted
- 10 Apr 2024 (actual)
- Results
- Posted 27 Mar 2026
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 randomized, controlled, six-way crossover clinical study to characterize the nicotine PK (pharmacokinetic) and subjective effects of HTPs (Heated Tobacco Products) comprised of 2 menthol varieties and 2 tobacco flavor varieties (Ploom® HTPs, Japan Tobacco Inc.) in adult menthol and non-menthol combustible cigarette smokers (males and females between the ages of 22 and 65). The study will include participants' UBCC (Usual Brand Combustible Cigarette) and a nicotine gum (Nicorette®) as high and low abuse liability reference products, respectively, to the HTP. Study participation is expected to last up to 34 days, including a 28-day screening period (that includes a 5-day at-home HTP product trial period), and a 6-day in-clinic confinement period (from Check-in [Day -1] through the end-of-study [EOS] visit on Day 6).
Detailed description
This is a randomized, controlled, six-way crossover clinical study to characterize the nicotine PK and subjective effects of HTPs (2 menthol varieties, Products A and B; 2 tobacco flavor varieties, Products C and D) in adult menthol and non-menthol combustible cigarette smokers. The study will include participants' UBCC (Product F) and a nicotine gum (Product E) as high and low abuse liability reference products, respectively, to the HTP.
Product A: Ploom® 3.1 HTP - Menthol HTS; MX3 (681) Product B: Ploom® 3.1 HTP - Menthol HTS; MX5 (706) Product C: Ploom® 3.1 HTP - Tobacco HTS; R8 (120) Product D: Ploom® 3.1 HTP - Tobacco HTS; RX4 (953) Product E: Nicorette® 4 mg Mint Nicotine Gum Product F: Combustible Cigarette (menthol or non-menthol), participant's usual brand
The study will include generally healthy adult males and females who smoke factory manufactured combustible cigarettes. This study will recruit approximately 60 participants (composed of approximately 30 menthol and 30 non-menthol adult smokers) in an attempt to obtain approximately 48 study completed participants (approximately 24 menthol and 24 non-menthol smokers). Adult participants will be between 22 and 65 years of age at screening, inclusive. Participants must have a history of smoking ≥ 10 to ≤ 30 menthol or non-menthol cigarettes daily for at least 12 months prior to screening.
Enrolled participants will be randomized based on sex and their UBCC (menthol or non-menthol) to one of 6 product use sequences.
Screening will occur within 28 days prior to Day 1 and includes administering the FTCD (Fagerstrom Test for Cigarette Dependence), standard safety procedures, collection of baseline information, and a 5-day at-home HTP product trial period.
Enrollment visit (Day -6) will occur 5 days prior to Check-in (Day -1). Participants will receive the Ploom® HTP products for at-home product acclimation to become familiar with the product during the next 5 days. Training on how to use the Ploom® HTP device will be provided to each participant at the Enrollment visit. Participants will receive all four varieties of HTS on Day -6 and begin the at-home product trial. Participants are required to use each HTS variety at least once a day ad libitum for a minimum of 20 HTS uses over 5 days.
Participants will check-in on the morning of Day -1. Product use sequence randomization and assignment will also occur on Day -1. Participants will be randomized based on sex and their UBCC (menthol or non-menthol) to one of six product use sequences. Once participants are randomized to a product use sequence, product use sessions in confinement will start. Participants will remain in confinement at the clinic until completion of all study activities on Day 6.
Starting on Day -1 (following Check-in) through Day 5, depending on the randomized product use sequence, participants will use their assigned product (HTP, UBCC, or nicotine gum) during an afternoon product use session. Participants will use the same assigned product to be tested during the next day's morning ad libitum product use PK test session (e.g., if a participant is assigned to Product A [HTP] as the product to be used in the morning ad libitum product use PK test session on Day 1, the participant will use Product A [HTP] during the afternoon product use session on Day -1). The afternoon product use session should be no more than approximately 6 hours long. Participants will be required to use the assigned study product at least once, but no more than six HTS, UBCC, or nicotine gum ad libitum per daily afternoon product use sessions. Participants will then be required to abstain from any tobacco- or nicotine-containing products for at least 12 hours prior to the start of the following morning's ad libitum product use PK test session. Morning ad libitum product use PK test sessions will occur on the mornings of Days 1, 2, 3, 4, 5, and 6 (for a total of 6 morning ad libitum product use PK test sessions).
During the morning ad libitum product use PK test session, participants will use the assigned study product per their assigned product use sequence. Participants will use a single UBCC or HTP for 5 minutes ad libitum or use the nicotine gum for 30 minutes per product use instruction. Blood samples for PK will be collected prior to and for 3 hours following the start of each morning ad libitum product use PK test session. Heart rate measurements will be taken at specified time points during each morning ad libitum product use PK test session. In addition, participants will complete subjective effects questionnaires (Product Liking, Tobacco/Nicotine Withdrawal, Direct Effects of Product, Use Product Again, and mCEQ) at designated time points during each morning ad libitum product use PK test session. Participants will remain in confinement starting with Check-in on Day -1 until discharge after all study activities are completed on Day 6. Participants will not be forced to use the tobacco/nicotine products at any time during the study.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 6
- Model description
- A randomized, controlled, six-way crossover clinical study to characterize the nicotine PK and subjective effects of HTPs (2 menthols, Products A and B; 2 tobacco flavors, Products C and D). Reference products include participants' UBCC (Product F) and nicotine gum (Product E). On Day -1 participants who completed the at-home study product trial and meet all inclusion/ exclusion criteria to be randomized at 1:1:1:1:1:1 ratio into 1 of 6 sequences in a 6x6 Latin Square Design as listed below: Sequence 1 = ABFCED; Sequence 2 = BCADFE; Sequence 3 = CDBEAF; Sequence 4 = DECFBA; Sequence 5 = EFDACB; Sequence 6 = FAEBDC. Product A: Ploom® 3.1 HTP - Menthol HTS; MX3 (681); Product B: Ploom® 3.1 HTP - Menthol HTS; MX5 (706); Product C: Ploom® 3.1 HTP - Tobacco HTS; R8 (120); Product D: Ploom® 3.1 HTP - Tobacco HTS; RX4 (953); Product E: Nicorette® 4 mg Mint Nicotine Gum; Product F: Combustible Cigarette (menthol or non-menthol), participant's usual brand
| Arm | Type | Receives |
|---|---|---|
| Randomization Sequence 1: ABFCED | Experimental | Other: Product A, Other: Product B, Other: Product C, Other: Product D, Other: Product E, Other: Product FUsage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order: Product A Product B Product F Product C Product E Product D |
| Randomization Sequence 2: BCADFE | Experimental | Other: Product A, Other: Product B, Other: Product C, Other: Product D, Other: Product E, Other: Product FUsage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order: Product B Product C Product A Product D Product F Product E |
| Randomization Sequence 3: CDBEAF | Experimental | Other: Product A, Other: Product B, Other: Product C, Other: Product D, Other: Product E, Other: Product FUsage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order: Product C Product D Product B Product E Product A Product F |
| Randomization Sequence 4: DECFBA | Experimental | Other: Product A, Other: Product B, Other: Product C, Other: Product D, Other: Product E, Other: Product FUsage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order: Product D Product E Product C Product F Product B Product A |
| Randomization Sequence 5: EFDACB | Experimental | Other: Product A, Other: Product B, Other: Product C, Other: Product D, Other: Product E, Other: Product FUsage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order: Product E Product F Product D Product A Product C Product B |
| Randomization Sequence 6: FAEBDC | Experimental | Other: Product A, Other: Product B, Other: Product C, Other: Product D, Other: Product E, Other: Product FUsage of study products in controlled use and ad libitum use sessions during the 6-day in-clinic period in following order: Product F Product A Product E Product B Product D Product C |
Who may qualify
- Ages
- 22 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Participants must be informed of the nature and risks of the study and voluntarily give written informed consent prior to screening.
- Healthy adult males and females ≥ 22 and ≤ 65 years of age, inclusive, at screening.
- Participants must self-report currently smoking menthol or non-menthol factory manufactured combustible cigarettes. Participants will have a history of smoking ≥ 10 to
- ≤ 30 menthol or non-menthol factory manufactured combustible cigarettes daily for at least 12 months prior to screening. Prior to screening, brief periods (i.e., up to 7 consecutive days) of non-smoking within 90 days before Check-in (e.g., due to illness or participation in a clinical study where tobacco use was prohibited) will not be exclusionary at the discretion of the Investigator (other non-daily tobacco use, except for heated tobacco use, within 30 days prior to screening are not exclusionary).
- Participants must be generally healthy, free of lifetime malignant tumors, and without clinically significant abnormalities as assessed by the Investigator based on the review of medical and surgical history, physical examination, vital signs, 12-lead ECG, and laboratory evaluations conducted at screening and Check-in, as applicable (refer to Table 1). A single repeat measurement/test may be performed to confirm vital signs, 12-lead ECG, and clinical laboratory tests abnormalities (i.e., to confirm that a participant is eligible).
Key exclusion criteria (31 listed)
- Use of any HTPs within the past 30 days prior to the screening visit; occasional use (i.e., not daily use) of other types of tobacco- or nicotine-containing products other than factory manufactured combustible cigarettes (e.g., roll-your-own cigarettes, e-cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) are allowed within the past 30 days prior to screening.
- Any postponement of a quit attempt to participate in the study; or any attempts to quit smoking in the 3 months prior to Day -1 (Check-in).
- Self-reported puffers (i.e., smokers who draw smoke from the combustible cigarette into the mouth and throat but do not inhale).
- Poor dentition that prevents participant from using nicotine gum.
- History or presence of any type of malignant tumor or clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other condition that, in the opinion of the Investigator, would interfere with the absorption, distribution, metabolism, or excretion of cotinine or jeopardize the safety of the participant or impact the validity of the study results.
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 AAlso: Ploom® 3.1 HTP - Menthol HTS; MX3 (681)Use of Product A in controlled use and ad libitum use sessions | Other | Randomization Sequence 1: ABFCED, Randomization Sequence 2: BCADFE, Randomization Sequence 3: CDBEAF, Randomization Sequence 4: DECFBA, Randomization Sequence 5: EFDACB, Randomization Sequence 6: FAEBDC |
| Product BAlso: Ploom® 3.1 HTP - Menthol HTS; MX5 (706)Use of Product B in controlled use and ad libitum use sessions | Other | Randomization Sequence 1: ABFCED, Randomization Sequence 2: BCADFE, Randomization Sequence 3: CDBEAF, Randomization Sequence 4: DECFBA, Randomization Sequence 5: EFDACB, Randomization Sequence 6: FAEBDC |
| Product CAlso: Ploom® 3.1 HTP - Tobacco HTS; R8 (120)Use of Product C in controlled use and ad libitum use sessions | Other | Randomization Sequence 1: ABFCED, Randomization Sequence 2: BCADFE, Randomization Sequence 3: CDBEAF, Randomization Sequence 4: DECFBA, Randomization Sequence 5: EFDACB, Randomization Sequence 6: FAEBDC |
| Product DAlso: Ploom® 3.1 HTP - Tobacco HTS; RX4 (953)Use of Product D in controlled use and ad libitum use sessions | Other | Randomization Sequence 1: ABFCED, Randomization Sequence 2: BCADFE, Randomization Sequence 3: CDBEAF, Randomization Sequence 4: DECFBA, Randomization Sequence 5: EFDACB, Randomization Sequence 6: FAEBDC |
| Product EAlso: Nicorette® 4 mg Mint Nicotine GumUse of Product E in controlled use and ad libitum use sessions | Other | Randomization Sequence 1: ABFCED, Randomization Sequence 2: BCADFE, Randomization Sequence 3: CDBEAF, Randomization Sequence 4: DECFBA, Randomization Sequence 5: EFDACB, Randomization Sequence 6: FAEBDC |
| Product FAlso: Combustible Cigarette (menthol or nonmenthol), participant's usual brandUse of Product F in controlled use and ad libitum use sessions | Other | Randomization Sequence 1: ABFCED, Randomization Sequence 2: BCADFE, Randomization Sequence 3: CDBEAF, Randomization Sequence 4: DECFBA, Randomization Sequence 5: EFDACB, Randomization Sequence 6: FAEBDC |
Primary outcome
Baseline-adjusted Plasma Nicotine Concentration Pharmacokinetic (PK) Parameters [Cmax] Assessment
Time frame: from time zero (defined as the start of product use) to 180 minutes post-use on each Day 1 through Day 6
Characterize PK parameters of nicotine in plasma during and after a single ad libitum use of HTP (two menthol and two tobacco flavor varieties) test products relative to UBCC and the nicotine gum reference products. Cmax: Maximum measured plasma concentration over the duration of the measurement interval from time zero (defined as the start of product use) to 180 minutes post-use on each Study Day 1 through Day 6.
Baseline-adjusted Plasma Nicotine Concentration Pharmacokinetic (PK) Parameter [AUC(0-180)] Assessment
Time frame: from time zero (defined as the start of product use) to 180 minutes post-use on each Study Day 1 through Day 6
Characterize PK parameters of nicotine in plasma during and after a single ad libitum use of HTP (two menthol and two tobacco flavor varieties) test products relative to UBCC and the nicotine gum reference products. AUC(0-180): Area under the nicotine concentration-time curve calculated using linear trapezoidal summation from time zero (defined as the start of product use) to 180 minutes post-use on each Study Day 1 through Day 6.
Baseline-adjusted Plasma Nicotine Concentration Pharmacokinetic (PK) Parameter [Tmax] Assessment
Time frame: Day 1 through Day 6
Characterize PK parameters of nicotine in plasma during and after a single ad libitum use of HTP (two menthol and two tobacco flavor varieties) test products relative to UBCC and the nicotine gum reference products. Tmax: Time of the maximum measured plasma concentration over the duration of the measurement interval.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites 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 Tobacco Use, run by Altria Client Services LLC at 3 sites 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 22 inclusion and 31 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: finished, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Yes. Results are posted in the registry (first posted 27 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline-adjusted Plasma Nicotine Concentration Pharmacokinetic (PK) Parameters [Cmax] Assessment (time frame: from time zero (defined as the start of product use) to 180 minutes post-use on each Day 1 through Day 6). The study lists 3 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 27 Mar 2026.