NCT07323511

Abuse Liability for Eight Electronic Nicotine Products

An Open-Label, Randomized, 8-way Crossover Study to Assess Elements of Abuse Liability of Electronic Nicotine Delivery System Products in Adult Smokers

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: RAI Services Company · Industry
• Sex: All
• Age: 21 Years – 60 Years
• Healthy volunteers: Accepted

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.

Detailed description

Adult smokers of filtered menthol and/or non-menthol cigarettes and smokers who also use ENDS will be recruited into this study to evaluate elements of ENDS IP AL, in comparison to participant's usual brand (UB) cigarette and nicotine polacrilex gum. 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 10-day, 9-night confinement period. On study Day 1, participants will enter a product familiarization period during which they will be required to use three ENDS IP (Products B,, Product D Product F, and nicotine gum (Product N) at least once. Use of each product during familiarization period will be approximately 5 minutes for each ENDS IP and approximately 30 minutes for a single piece of nicotine gum. After completing this familiarization, they 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 2 and each day prior to a test session) during which they will use their randomized IP (excluding their UB cigarette) assigned for use in the next day's test session at least four times, for approximately 5 minutes per use for ENDS IPs and approximately 30 minutes for a single piece of nicotine gum use. 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 3 and continuing through Day 10, each participant will participate in eight consecutive daily test sessions, evaluating one IP per session. Over the course of the study, each participant will evaluate a total of eight IPs: six ENDS IPs, a high-AL comparator (the participant's UB cigarette), and a low- AL comparator (a commercially available nicotine replacement therapy \[NRT\] nicotine gum). During each test session, blood samples will be collected for plasma nicotine PK assessments. Additionally, subjective effects questionnaire responses and physiological measures will be taken before, during, and after each product use. The active period of each test session will start with assigned IP use initiation and last approximately 4 hours during and following product use. During each test session, participants will be allowed approximately 5 minutes of smoking one UB cigarette; approximately 5 minutes of ENDS IP use; or approximately 30 minutes of nicotine gum use (one piece per package labeling), based on the product use sequence to which participants will be randomized. Participants' use of the ENDS IP 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. ENDS IP cartridges will be weighed within 4 hours before and after the test session on Days 3 - 10. Participant safety 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.

Conditions

• Smoking
• Smoking Behaviors
• Tobacco Use
• Tobacco Smoking

Interventions

Type	Name	Description
OTHER	Product A	Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette
OTHER	Product B	Tobacco Flavor, 5%
OTHER	Product C	Tobacco Flavor, 1.5%
OTHER	Product D	Tobacco Flavor, 5%
OTHER	Product E	Tobacco Flavor, 2.4%
OTHER	Product F	Tobacco Flavor, 5%
OTHER	Product G	Mint Flavor, 5%
OTHER	Product N	Nicorette® White Ice Mint 4 mg nicotine polacrilex gum

Timeline

• Start date: 2026-02-15
• Primary completion: 2026-04-15
• Completion: 2026-09-15
• First posted: 2026-01-07
• Last updated: 2026-01-07