NCT07323511

Brief Summary

This will be a randomized, open-label, 8-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 \[PK\]) during and following ad libitum use of Electronic Nicotine Delivery System (ENDS) investigational products (IPs) in a confinement setting by generally healthy adult smokers of combustible cigarettes and dual users of cigarettes and ENDS products.

Trial Health

65
Monitor

Trial Health Score

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

Enrollment
70

participants targeted

Target at P50-P75 for not_applicable

Timeline
4mo left

Started Feb 2026

Shorter than P25 for not_applicable

Status
not yet recruiting

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 Progress39%
Feb 2026Sep 2026

First Submitted

Initial submission to the registry

December 22, 2025

Completed
16 days until next milestone

First Posted

Study publicly available on registry

January 7, 2026

Completed
1 month until next milestone

Study Start

First participant enrolled

February 15, 2026

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 15, 2026

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 15, 2026

Expected
Last Updated

January 7, 2026

Status Verified

December 1, 2025

Enrollment Period

2 months

First QC Date

December 22, 2025

Last Update Submit

December 22, 2025

Conditions

Outcome Measures

Primary Outcomes (2)

  • AUECPL 3-240

    area under the effect curve (AUEC) for PL (VAS score-versus-time)

    3 minutes to 240 minutes

  • Emax PL

    maximum effect (maximum PL VAS score after the start of IP use)

    240 minutes

Study Arms (8)

Product usage order ANBGCFDE

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order BACNDGEF

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order CBDAENFG

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order DCEBFAGN

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order EDFCGBNA

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order FEGDNCAB

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order GFNEADBC

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Product usage order NGAFBECD

EXPERIMENTAL

Subjects will use each of the 8 products during an evaluation period, followed by a 4 hour Test Session

Other: Product AOther: Product BOther: Product COther: Product DOther: Product EOther: Product FOther: Product GOther: Product N

Interventions

Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette

Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Tobacco Flavor, 5%

Also known as: P2815222
Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Tobacco Flavor, 1.5%

Also known as: P2815216
Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Tobacco Flavor, 5%

Also known as: P29156222
Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Tobacco Flavor, 2.4%

Also known as: P2615222
Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Tobacco Flavor, 5%

Also known as: P2615217
Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Mint Flavor, 5%

Also known as: P2915322
Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Nicorette® White Ice Mint 4 mg nicotine polacrilex gum

Product usage order ANBGCFDEProduct usage order BACNDGEFProduct usage order CBDAENFGProduct usage order DCEBFAGNProduct usage order EDFCGBNAProduct usage order FEGDNCABProduct usage order GFNEADBCProduct usage order NGAFBECD

Eligibility Criteria

Age21 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Able to read, understand, and willing to sign an informed consent form (ICF) and complete questionnaires written in English.
  • Generally healthy male or female, 21 to 60 years of age, inclusive, at the time of consent.
  • Expired breath carbon monoxide level is ≥ 10 ppm and ≤ 100 ppm at Screening.
  • Positive (≥200 ng/ml) urine cotinine test at Screening.
  • Smokes only combustible filtered, menthol or non-menthol cigarettes, 83 mm to 100 mm in length.
  • Agrees to smoke same UB cigarette throughout the study period. UB cigarette is defined as the cigarette brand style currently smoked most frequently by the participant.
  • Participants must meet one (a or b) of the following tobacco use conditions:
  • Smokes 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 the Principal Investigator (PI).
  • 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 the PI 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.
  • 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 only UB cigarette, ENDS IPs, and nicotine gum during the study period.
  • Willing to abstain from tobacco and nicotine use for at least 12 hours prior to each test session.
  • Females must be willing to use a form of contraception acceptable to the PI from the time of signing informed consent until End-of-Study.
  • 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.
  • +1 more criteria

You may not qualify if:

  • 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 the PI, makes the study participant unsuitable to participate in this clinical study.
  • History, presence of, or clinical laboratory test results indicating diabetes.
  • 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.
  • Weight of ≤ 110 pounds at Screening.
  • Hemoglobin level is \< 12.5 g/dL for females or \<13.0 g/dL for males at Screening.
  • 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 the PI's discretion.
  • Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
  • 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.
  • Must not be a current regular user (i.e., \> 5 times per month) of any tobacco products other than cigarettes or ENDS within the last 6 months prior to screening.
  • 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.
  • History or presence of bleeding or clotting disorders.
  • Use of daily aspirin (≥ 325 mg) or other daily anticoagulants.
  • 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.
  • Plasma donation within ≤ 7 days prior to the signing of informed consent and between Screening and check-in Day 1.
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

SmokingTobacco UseTobacco Smoking

Interventions

HTR3D protein, human

Condition Hierarchy (Ancestors)

Behavior

Study Officials

  • Milly Kanobe

    Reynolds American

    STUDY DIRECTOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 22, 2025

First Posted

January 7, 2026

Study Start

February 15, 2026

Primary Completion

April 15, 2026

Study Completion (Estimated)

September 15, 2026

Last Updated

January 7, 2026

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share