Pharmacokinetic and Subjective Effects of Heated Tobacco Products

Inclusion Criteria

• Participants must be informed of the nature and risks of the study and voluntarily give written informed consent prior to screening.
• Healthy adult males and females ≥ 22 and ≤ 65 years of age, inclusive, at screening.
• Participants must self-report currently smoking menthol or non-menthol factory manufactured combustible cigarettes. Participants will have a history of smoking ≥ 10 to

≤ 30 menthol or non-menthol factory manufactured combustible cigarettes daily for at least 12 months prior to screening. Prior to screening, brief periods (i.e., up to 7 consecutive days) of non-smoking within 90 days before Check-in (e.g., due to illness or participation in a clinical study where tobacco use was prohibited) will not be exclusionary at the discretion of the Investigator (other non-daily tobacco use, except for heated tobacco use, within 30 days prior to screening are not exclusionary).

• Participants must be generally healthy, free of lifetime malignant tumors, and without clinically significant abnormalities as assessed by the Investigator based on the review of medical and surgical history, physical examination, vital signs, 12-lead ECG, and laboratory evaluations conducted at screening and Check-in, as applicable (refer to Table 1). A single repeat measurement/test may be performed to confirm vital signs, 12-lead ECG, and clinical laboratory tests abnormalities (i.e., to confirm that a participant is eligible).
• Screening and Check-in systolic/diastolic blood pressure ≤ 150/90 mmHg measured after being seated quietly for at least 10 minutes. Two rechecks may be performed at the Investigator's discretion.
• Urine cotinine ≥ 500 ng/mL at screening.
• Exhaled carbon monoxide ≥ 10 ppm at screening.
• Negative pregnancy test at screening and Check-in (Day -1) for all female participants.
• Female participants who are sexually active and of childbearing potential (i.e., not surgically sterile at least 6 months prior to Check-in nor post-menopausal with amenorrhea for at least 1 year prior to Check-in and FSH levels consistent with postmenopausal status) must not be lactating and must have been using one of the following forms of contraception from 3 months before first study product administration through 30 days after the final administration of study product:
• hormonal (e.g., oral, vaginal ring, transdermal patch, implant, injection) consistently for at least 3 months prior to Check-in, when used in combination with male condoms with spermicide (use of NuvaRing® is at the Investigator's discretion)
• double barrier (e.g., condom with spermicide or diaphragm with spermicide) consistently for at least 2 weeks prior to Check-in
• intrauterine device or system (utilize Investigator discretion regarding use of hormonal or nonhormonal devices) for at least 3 months prior to Check-in
• exclusive partner who is clinically sterile (i.e., documented infertility or surgical sterilization; see below for additional information on sterility) or has been vasectomized for at least 6 months (inclusive) prior to Check-in Note: Sexual abstinence, defined as refraining from intercourse, is allowed when this is in line with the preferred and usual lifestyle of the participant. Female participants of childbearing potential who are not currently engaging in heterosexual intercourse must agree to use one of the above methods of birth control through completion of study, in the event that they have heterosexual intercourse during the course of the study.
• Female participants who are of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to Check-in:
• hysteroscopic sterilization with documentation of success with hysterosalpingogram
• bilateral tubal ligation or bilateral salpingectomy
• hysterectomy
• bilateral oophorectomy
• Essure® or be post-menopausal with amenorrhea for at least 1 year prior to Check-in and confirmed by FSH levels consistent wi