Abuse Liability for Four Heated Tobacco Product (HTP) Consumables and Two HTP Devices

NCT07267195 | Not Yet Recruiting

• 1 other identifier: CSD252501
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-site, open-label, randomized, 8-way crossover study designed to evaluate elements of abuse liability (AL), including subjective effects and physiological measures (pharmacodynamics \[PD\]) and plasma nicotine uptake (pharmacokinetics \[PK\]), during and following ad libitum use of the study investigational products (IPs) by generally healthy adult smokers.

Conditions

Smoking; Smoking Behaviors; Tobacco Use; Tobacco Smoking

Outcome Measures

Primary Outcomes (2)

• AUECPL 3-240

  area under the curve (AUEC) for PL (VAS score-versus-time) from 3 minutes to 240 minutes after the start of IP use

  3 minutes to 240 minutes

• Emax PL

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

  240 minutes

Study Arms (2)

Tobacco

EXPERIMENTAL

Eligible participants will be randomized to one of 8 IP use sequences, such that one of the following IPs (A, B, C, D, E, F, G, N) will be used in each of the eight test sessions:

Other: Product A; Other: Product N; Other: Product B; Other: Product C; Other: Product D; Other: Product E; Other: Product F; Other: Product G

Menthol

EXPERIMENTAL

Eligible participants will be randomized to one of 8 IP use sequences, such that one of the following IPs (A, H, I, J, K, L, M, N) will be used in each of the eight test sessions:

Other: Product A; Other: Product N; Other: Product H; Other: Product I; Other: Product J; Other: Product K; Other: Product L; Other: Product M

Interventions

Product A OTHER

Usual Brand filtered, non-menthol /menthol combustible cigarette

Menthol; Tobacco

Product N OTHER

Nicorette White Ice Mint 4 mg

Menthol; Tobacco

Product B OTHER

Signature Tobacco, Standard Mode, Device 1

Tobacco

Product C OTHER

Signature Tobacco, Boost Mode, Device 1

Tobacco

Product D OTHER

Roasted Tobacco, Standard Mode, Device 1

Tobacco

Product E OTHER

Signature Tobacco, Standard Mode, Device 2

Tobacco

Product F OTHER

Signature Tobacco, Boost Mode, Device 2

Tobacco

Product G OTHER

Roasted Tobacco, Standard Mode, Device 2

Tobacco

Product H OTHER

Fresh Menthol, Standard Mode, Device 1

Menthol

Product I OTHER

Fresh Menthol, Boost Mode, Device 1

Menthol

Product J OTHER

Menthol Capsule (Crushed), Standard Mode, Device 1

Menthol

Product K OTHER

Fresh Menthol, Standard Mode, Device 2

Menthol

Product L OTHER

Fresh Menthol, Boost Mode, Device 2

Menthol

Product M OTHER

Menthol Capsule (Crushed), Standard Mode, Device 2

Menthol

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (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 males or females, 21 to 60 years of age, inclusive, at the time of consent.
• Smokes combustible, filtered, non-menthol (Arm 1 only) or menthol cigarettes (Arm 2 only), 83 mm to 100 mm in length as primary source of tobacco. Smokers who also use other tobacco products (e.g., ENDS, smokeless tobacco, HTPs) will not be excluded from study participation,
• Smokes an average of at least 10 cigarettes per day (CPD) and inhales the smoke, for at least 6 months prior to Screening. Brief periods of abstinence due to illness, quit attempt (prior to 30 days of Screening), or clinical study participation (prior to 30 days of Screening) will be allowed at the discretion of the PI.
• Agrees to smoke the same UB cigarette throughout the study period. The UB cigarette is defined as the reported cigarette brand and style currently smoked most frequently by the participant.
• Expired breath carbon monoxide (ECO) level is ≥ 10 ppm and ≤ 100 ppm at Screening and at check-in (Day -1).
• Positive urine cotinine test (e.g., \>200 ng/mL) via dipstick at Screening.
• Response at Screening to the Fagerström Test for Nicotine Dependence (FTND) Question 1 ("How soon after you wake up do you smoke your first cigarette?") is either "Within 5 minutes" or "6-30 minutes" (Heatherton et al., 1991).
• Willing to use the UB cigarette, Study IPs, and Nicorette® nicotine gum during the study period.
• Willing to abstain from tobacco and nicotine use for at least 12 hours prior to the start of each of four Test Sessions.
• Females must be willing to use a form of contraception acceptable to the PI from the time of signing the ICF until End-of-Study.
• Examples of acceptable means of birth control are, but not limited to:
• Surgical sterilization (hysterectomy, bilateral tubal ligation/occlusion, bilateral
• oophorectomy, bilateral salpingectomy);
• physical barrier method (e.g., condom, diaphragm/sponge/cervical cap) with

You may not qualify if:

• Individuals or their family members that have ongoing litigation with tobacco company(ies).
• 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.
• 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.
• History or presence of bleeding or clotting disorders.
• Any history of cancer, except for primary cancers of skin such as localized basal cell/squamous cell carcinoma that has been surgically and/or cryogenically removed.
• Systolic BP of \> 160 mmHg or a diastolic BP of \> 95 mmHg, measured after being seated for 5 minutes at Screening or at check-in Day -1.
• Weight of \> 50.0 kg at Screening.
• Hemoglobin level is \> 12.5 g/dL for females or \> 13.0 g/dL for males at Screening.
• Females who have a positive pregnancy test, are pregnant, breastfeeding, or intend to become pregnant during the course of the study.
• Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV).
• Use of any medication or substance that aids in smoking cessation, including but not limited to any NRT (e.g., nicotine gum, lozenge, patch), varenicline (Chantix®), bupropion (Wellbutrin®, Zyban®), GLP-1 agonists (e.g., Mounjaro®, Ozempic®, Wegovy®), or lobelia extract within (≤) 30 days prior to signing the informed consent.
• Postpones a decision to quit using tobacco- or nicotine-containing products in order to participate in this study or self-reports a previous quit attempt within (≤) 30 days prior to signing the informed consent.
• Any use of daily aspirin (≥ 325 mg) or any use of other anticoagulants.
• Individuals ≥ 35 years of age currently using systemic, testosterone, estrogen-containing contraception or hormone replacement therapy.

Sponsors & Collaborators

• RAI Services Company: lead

MeSH Terms

Conditions

Smoking; Tobacco Use; Tobacco Smoking

Interventions

HTR3D protein, human

Condition Hierarchy (Ancestors)

Behavior

Study Officials

• Brian Keyser

  Reynolds American

  STUDY DIRECTOR

Central Study Contacts

John Darnell

CONTACT

3367410386; darnelj2@rjrt.com

Kristen Prevette

CONTACT

prevetk1@rjrt.com

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: November 24, 2025
• First Posted: December 5, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share