This is a single-site, open-label, randomized, 4-way cross-over study designed to evaluate elements of abuse liability (AL) including subjective effects and physiological measures (pharmacodynamics \[PD\]) and plasma nicotine uptake (pharmacokinetics \[PK\]) during controlled monitored use and following ad libitum use of the study investigational products (IPs) by generally healthy smokers who are also users of smokeless tobacco.
Smokers who only use filtered menthol or non-menthol cigarettes and who also use loose or pouched moist snuff smokeless tobacco \[Smokeless Tobacco (MST)\] will be recruited into this AL study to evaluate elements of AL of two modern oral nicotine products (hereinafter, Study IPs) compared to combustible cigarettes (CC) and moist snuff tobacco. Potential participants will complete a pre-screening telephone interview. They will complete a Screening Visit to assess their eligibility within 45 days prior to check-in and enrollment. Starting on Day 1, participants will check-in at the clinical site to confirm eligibility. Eligible participants will be enrolled, randomized and confined in the clinic for 5 days (4 nights). Participants will be randomized to a product use sequence (using a Williams Design) in which they will evaluate one IP in each of four separate daily Test Sessions, such that each participant will evaluate four IPs; Product B-A 9 mg, Product C-B 9 mg, participant's usual brand moist snuff tobacco \[UB MST\], and a high-AL comparator (participant's usual brand \[UB\] cigarette). On Day 2 and continuing through Day 5, participants will participate in daily Test Sessions that will last approximately 8 hours, consisting of a 1-hour first use session immediately followed by a 7-hour ad libitum session. Each Test Session will include collection of both types of PD measures (subjective and physiological) and PK measures prior to, during, and following IP use. Following each test session, used IP (MO and UB MST pouched IPs only) will be collected, stored at -20°C, and shipped to a laboratory of the sponsor's choosing. For participants whose UB MST is loose moist snuff tobacco, a fresh unopened tin/can will be weighed immediately prior to the 'first use' portion of the session before the participant self-selects the amount of loose MST for their initial IP use. The lid will be replaced on the can/tin and weighed to the nearest 0.01g. Immediately following the 1-hour 'first use' portion of the test session, a 7-hour ab libitum period will commence. Both types of PD (subjective and physiological) and PK measures will be measured during the 7-hour ab libitum period. The number, time, and duration of use of IPs that participants request will be recorded; every used IPs (MO and UB MST pouched IPs only) will be collected, stored at -20°C, and shipped to a laboratory of the sponsor's choosing. For participants whose UB MST is loose moist snuff, a fresh unopened tin/can will be weighed immediately prior to the participant self-selects the amount of loose UB MST for their test session, then the lid will be replaced to the can/tin and weighed to the nearest 0.01g. It is permissible to use the tin/can that was used for the earlier test session. On the half day prior to each respective Test Session, a Product Acclimation Period will allow participants ad libitum use of the subsequent IP (at least two trial uses), except the participant's UB CC and UB MST, as per randomized sequence for product acclimation prior to use in the next day's Test Session. Participants can also use their UB cigarettes ad libitum, until the 12-hour tobacco and nicotine abstinence period begins prior to each Test Session, as long as the minimum use requirement for randomized IP is met. Used IP (only MO IPs and UB moist pouched snuff) from each of the Product Acclimation periods will be collected, stored at -20°C, and shipped to a laboratory of the sponsor's choosing. Safety will be monitored throughout the study by the Principal Investigator (PI) (or designee) by assessing adverse experiences/events (AEs), vital sign measurements, physical examinations (including an oral examination), and clinical laboratory tests. The Medical Monitor will be available for consultation during the study and for any follow-ups after study discharge.
Usual Brand (UB) filtered, menthol or non-menthol combustible cigarette
-A 9 mg Nicotine
-B 9 mg Nicotine
AUECPL 5-60
area under the effect curve (AUEC) for PL (VAS score-versus-time)
Time frame: 5 minutes to 60 minutes
Emax PL
maximum effect (maximum PL VAS score after the start of IP use)
Time frame: 60 minutes
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
40
UB loose or pouched moist snuff