This is a randomized, controlled, open-label, 6 parallel arms study to assess reduced exposure of biomarkers of exposure (BoE) of selected HPHC in smokers switching to TP18 (a prototype heated tobacco device) or THS relative to smokers who continue smoking CIG after 5 days of confinement period, followed by 2 days of pharmacokinetic (PK) period of single use of THS/TP18 and CIG, and followed by an ambulatory period.
This randomized, controlled, open-label study comprises six parallel arms and is designed to evaluate reductions in biomarkers of exposure (BoE) to selected HPHCs in adult smokers switching toTP18 (a prototype heated tobacco device with four variants: THS1, THS2, THS3, THS4) or THS5 relative to smokers who continue smoking CIG after 5 days of confinement period followed by 2 days of pharmacokinetic (PK) period of single use of THS/TP18 and CIG, and followed by an ambulatory period. During the 5-day confinement period, participants will be randomized to use only their assigned product and will operate their assigned devices (THS1, THS2, THS3, THS4, or THS5) with their corresponding sticks or continue smoking CIG ad libitum (6 arms in total). In the subsequent 2-day PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. Participants randomized to the CIG arm at Baseline will not participate in this period. During the ambulatory period, participants randomized to one of the TP18 versions at Baseline will be free to choose and use any TP18 variant at any time, ad libitum. Participants randomized at Baseline to TP18 will continue using THS ad libitum. Participants randomized to the CIG arm will only be smoking cigarettes, ad libitum.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
108
TP18 prototype variant "1" (THS1) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants.
TP18 prototype variant "2" (THS2) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants.
TP18 prototype variant "3" (THS3) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants.
Celerion
Belfast, United Kingdom
RECRUITING3-hydroxypropyl mercapturic acid (3-HPMA) in Urine (confinement period)
Concentrations of 3-HPMA measured in 24-hour urine and expressed as concentration adjusted for creatinine.
Time frame: Measured from Day -1 to Day 5.
2-cyanoethyl mercapturic acid N-acetyl-S-(2-cyanoethyl)-L-cysteine (2-CyEMA) in Urine (confinement period)
Concentrations of 2-CyEMA measured in 24-hour urine and expressed as concentration adjusted for creatinine.
Time frame: Measured from Day -1 to Day 5.
Monohydroxybutenyl mercapturic acid (MHBMA) in Urine (confinement period)
Concentrations of MHBMA measured in 24-hour urine and expressed as concentration adjusted for creatinine.
Time frame: Measured from Day -1 to Day 5.
Total N-nitrosonornicotine (total NNN) in Urine (confinement period)
Concentrations of total NNN measured in 24-hour urine and expressed as concentration adjusted for creatinine.
Time frame: Measured from Day -1 to Day 5.
Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in Urine (confinement period)
Concentrations of total NNAL measured in 24-hour urine and expressed as concentration adjusted for creatinine.
Time frame: Measured from Day -1 to Day 5.
Carboxyhemoglobin (COHb) in Blood (confinement period)
Carboxyhemoglobin (COHb) is assayed from whole blood and expressed as percentage of the total hemoglobin saturated with carbon monoxide.
Time frame: Measured from Day -1 to Day 5.
S-phenylmercapturic acid (S-PMA) in Urine (confinement period)
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TP18 prototype variant "4" (THS4) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants.
THS 3.0 device (reference) and the corresponding tobacco sticks will be provided by the Sponsor. There are two variants of the sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants may choose either variant or both.
Current cigarette smokers will use their usual brand of commercially available CIG.
Concentrations of S-PMA measured in 24-hour urine and expressed as concentration adjusted for creatinine.
Time frame: Measured from Day -1 to Day 5.
2-hydroxyethylmercapturic acid (2-HEMA) in Urine (confinement period)
Concentrations of 2-HEMA measured in 24-hour urine and expressed as concentration adjusted for creatinine.
Time frame: Measured from Day -1 to Day 5.
3-hydroxy-1-methylpropylmercapturic acid (3-HMPMA) in Urine (confinement period)
Concentrations of 3-HMPMA measured in 24-hour urine and expressed as concentration adjusted for creatinine.
Time frame: Measured from Day -1 to Day 5.
Total 3-hydroxybenzo(a)pyrene (3-OH-B[a]P) in Urine (confinement period)
Concentrations of 3-OH-B\[a\]P measured in 24-hour urine and expressed as concentration adjusted for creatinine.
Time frame: Measured from Day -1 to Day 5.
4-aminobiphenyl (4-ABP) in Urine (confinement period)
Concentrations of 4-ABP measured in 24-hour urine and expressed as concentration adjusted for creatinine.
Time frame: Measured from Day -1 to Day 5.
2-aminonaphtalene (2-NA) in Urine (confinement period)
Concentrations of 2-NA measured in 24-hour urine and expressed as concentration adjusted for creatinine.
Time frame: Measured from Day -1 to Day 5.