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). The study will be conducted in a confinement setting among generally healthy adult smokers of combustible cigarettes and dual users of cigarettes and ENDS products.
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. 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 at the clinical site. On study Day -1, participants will enter a product familiarization period during which they will be required to use each of three ENDS IP (Product C \[Glacier Menthol 5%, device, 6.5W\], Product F \[Fresh Mint 5%, device, 6.5W\], and Product H \[Fresh Mint 5%, device, 6.5W\]) at least once. Use of each ENDS IP during the familiarization period will be approximately 5 minutes. After completing this familiarization, participants 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 1 and each day prior to a test session. During each daily product acclimation period, participants will be required to use their randomized IP assigned for use in the subsequent day's test session (excluding their UB cigarette) at least four times. For each ENDS IP, each product use period during the daily acclimation period will last approximately 5 minutes. 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 2 and continuing through Day 9, 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: seven ENDS IPs and a high-AL comparator (the participant's UB cigarette). During each test session, subjective effects questionnaire responses will be collected before, during, and after each product use. Blood samples will then be collected for plasma nicotine PK assessments, and, subsequently, the collection of physiological measures after IP use. Table 1-1 and Table 1-2 outline the schedule of study procedures, and the timing and sequence of activities involving behavioral questionnaires, PK blood sampling and physiological measurements, respectively. The active period of each test session will start with the 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 and approximately 5 minutes of ENDS IP use 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 e-liquid cartridges will be weighed within 4 hours before and after the test session on Days 2 - 9. Participant general health and well-being 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
50
Golden Tobacco Chill 5% (4) 6.5W
Glacier Menthol 5% (4) 6.5W
Fresh Mint 5% (4) 6.5W
Fresh Mint 5% (4) 4.5W
Fresh Mint 5% (3) 6.5W
Fresh Mint 5% (3) 5.5W
Fresh Mint 5% (2) 6.5W
Usual Brand Cigarette
AUC nic 3-240
Baseline-adjusted area under the plasma nicotine concentration-versus-time curve from time 3 to 240 minutes after the start of IP use
Time frame: 3 minutes to 240 minutes
Emax PL
maximum PL VAS score after the start of IP use
Time frame: 240 minutes
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