NCT06356610

Brief 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 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).

Trial Health

87
On Track

Trial Health Score

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

Enrollment
80

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Feb 2024

Geographic Reach
1 country

3 active sites

Status
completed

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 6, 2024

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

March 12, 2024

Completed
29 days until next milestone

First Posted

Study publicly available on registry

April 10, 2024

Completed
4 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 14, 2024

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 18, 2024

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

March 27, 2026

Completed
Last Updated

March 27, 2026

Status Verified

November 1, 2025

Enrollment Period

2 months

First QC Date

March 12, 2024

Results QC Date

November 18, 2025

Last Update Submit

March 9, 2026

Conditions

Keywords

TobaccoSmokingHeated tobacco

Outcome Measures

Primary Outcomes (3)

  • 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.

    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.

    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.

    Day 1 through Day 6

Other Outcomes (1)

  • Main Outcome of Product Liking Questionnaire Response VAS Score Parameter [Emax-PL] Assessment

    from 5 minutes to 180 minutes after the start of each morning ad libitum product use on Study Day 1 through Day 6

Study Arms (6)

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

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: 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

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: 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

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: 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

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: 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

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: 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

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product F

Interventions

Use of Product D in controlled use and ad libitum use sessions

Also known as: Ploom® 3.1 HTP - Tobacco HTS; RX4 (953)
Randomization Sequence 1: ABFCEDRandomization Sequence 2: BCADFERandomization Sequence 3: CDBEAFRandomization Sequence 4: DECFBARandomization Sequence 5: EFDACBRandomization Sequence 6: FAEBDC

Use of Product E in controlled use and ad libitum use sessions

Also known as: Nicorette® 4 mg Mint Nicotine Gum
Randomization Sequence 1: ABFCEDRandomization Sequence 2: BCADFERandomization Sequence 3: CDBEAFRandomization Sequence 4: DECFBARandomization Sequence 5: EFDACBRandomization Sequence 6: FAEBDC

Use of Product F in controlled use and ad libitum use sessions

Also known as: Combustible Cigarette (menthol or nonmenthol), participant's usual brand
Randomization Sequence 1: ABFCEDRandomization Sequence 2: BCADFERandomization Sequence 3: CDBEAFRandomization Sequence 4: DECFBARandomization Sequence 5: EFDACBRandomization Sequence 6: FAEBDC

Use of Product A in controlled use and ad libitum use sessions

Also known as: Ploom® 3.1 HTP - Menthol HTS; MX3 (681)
Randomization Sequence 1: ABFCEDRandomization Sequence 2: BCADFERandomization Sequence 3: CDBEAFRandomization Sequence 4: DECFBARandomization Sequence 5: EFDACBRandomization Sequence 6: FAEBDC

Use of Product B in controlled use and ad libitum use sessions

Also known as: Ploom® 3.1 HTP - Menthol HTS; MX5 (706)
Randomization Sequence 1: ABFCEDRandomization Sequence 2: BCADFERandomization Sequence 3: CDBEAFRandomization Sequence 4: DECFBARandomization Sequence 5: EFDACBRandomization Sequence 6: FAEBDC

Use of Product C in controlled use and ad libitum use sessions

Also known as: Ploom® 3.1 HTP - Tobacco HTS; R8 (120)
Randomization Sequence 1: ABFCEDRandomization Sequence 2: BCADFERandomization Sequence 3: CDBEAFRandomization Sequence 4: DECFBARandomization Sequence 5: EFDACBRandomization Sequence 6: FAEBDC

Eligibility Criteria

Age22 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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.
  • 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
  • +6 more criteria

You may not qualify if:

  • 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.
  • 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.
  • 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.
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Alliance for Multispecialty Research, LLC

Lexington, Kentucky, 40509, United States

Location

QPS Bio-Kinetic

Springfield, Missouri, 65802, United States

Location

Alliance for Multispecialty Research, LLC

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Conditions

Tobacco UseSmoking

Interventions

HTR3D protein, humanNicotine Chewing GumMenthol

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Chewing GumPlant GumsBiopolymersPolymersMacromolecular SubstancesPolysaccharidesCarbohydratesTobacco Use Cessation DevicesTherapeuticsCandyFoodDiet, Food, and NutritionPhysiological PhenomenaFood and BeveragesCyclohexanolsHexanolsFatty AlcoholsAlcoholsOrganic ChemicalsCyclohexane MonoterpenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsMonoterpenesTerpenesLipids

Results Point of Contact

Title
Jeffery Edmiston, ALCS Clinical Research, Functional Director
Organization
Altria

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Masking Details
Study participants will know when they are using their UBCC (usual brand combustible cigarette) and the nicotine gum. However, participants will not be informed of which Ploom® HTS (heated tobacco stick) product they are using. Participants will not see the stick or device packaging.
Purpose
OTHER
Intervention Model
CROSSOVER
Model Details: 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
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 12, 2024

First Posted

April 10, 2024

Study Start

February 6, 2024

Primary Completion

April 14, 2024

Study Completion

December 18, 2024

Last Updated

March 27, 2026

Results First Posted

March 27, 2026

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will not share

Locations