Nicotine Pharmacokinetic Study of Heated Tobacco and Heated Herbal Products

Study Overview
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Brief Summary
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This is a randomised, cross-over, open-label, confinement study conducted in 25 adult male or female smokers of combustible cigarettes (CCs). The study investigates combustible cigarettes, heated tobacco products (HTPs), and Heated Herbal Products (HHPs), with endpoints including pharmacokinetic evaluation, and subjective effects. Subjects will perform a Screening Visit and one Study Visit, including a 6-day confinement period.

Official Title
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A Randomised, Cross-Over, Nicotine Pharmacokinetic and Pharmacodynamic Study of Heated Tobacco and Heated Herbal Products Compared With Combustible Cigarettes

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Other: Pulze device with heated tobacco sticks (Product A)
* Other: Pulze device with heated tobacco sticks (Product B)
* Other: Pulze device with nicotine-infused heated herbal sticks (Product C)
* Other: Pulze device with nicotine-infused heated herbal sticks (Product D)
* Other: Conventional Cigarette (Product E)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Reports smoking an average of at least 10 manufactured combustible (menthol or non-menthol) cigarettes per day for at least 12 months prior to Screening Has a positive urine cotinine (>500 ng/mL) at Screening Has an exhaled carbon monoxide >10 ppm at Screening Female subjects of childbearing potential must use contraception Male subjects must use contraception Exclusion Criteria: Has a history or presence of clinically significant disease or condition that, in the opinion of the Investigator, would jeopardise the safety of the subject or impact the validity of the study results. Has a positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) at Screening Has a body mass index (BMI) > 30.0 kg/m^2 or < 18.0 kg/m^2 at Screening Has a fever (>38.05°C) at Screening or check-in Has a history or presence of drug or alcohol abuse within 24 months of Check-in Pregnant or lactating females Has used any prescription smoking cessation treatments within 3 months prior to Check-in Is planning to quit smoking during the study or within the next 3 months

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Product use sequence ABECD<br>Subjects use Product A on Day 1, Product B on Day 2, Product E on Day 3 and Product C on Day 4 and Product D on Day 5. | Other: Pulze device with heated tobacco sticks (Product A)<br>* Product A, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with heated tobacco sticks (Product B)<br>* Product B, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with nicotine-infused heated herbal sticks (Product C)<br>* Product C, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with nicotine-infused heated herbal sticks (Product D)<br>* Product D, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Conventional Cigarette (Product E)<br>* Subject's own brand combustible cigarette used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>|
| Experimental: Product use sequence BCADE<br>Subjects use Product B on Day 1, Product C on Day 2, Product A on Day 3 and Product D on Day 4 and Product E on Day 5. | Other: Pulze device with heated tobacco sticks (Product A)<br>* Product A, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with heated tobacco sticks (Product B)<br>* Product B, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with nicotine-infused heated herbal sticks (Product C)<br>* Product C, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with nicotine-infused heated herbal sticks (Product D)<br>* Product D, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Conventional Cigarette (Product E)<br>* Subject's own brand combustible cigarette used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>|
| Experimental: Product use sequence CDBEA<br>Subjects use Product C on Day 1, Product D on Day 2, Product B on Day 3 and Product E on Day 4 and Product A on Day 5. | Other: Pulze device with heated tobacco sticks (Product A)<br>* Product A, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with heated tobacco sticks (Product B)<br>* Product B, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with nicotine-infused heated herbal sticks (Product C)<br>* Product C, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with nicotine-infused heated herbal sticks (Product D)<br>* Product D, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Conventional Cigarette (Product E)<br>* Subject's own brand combustible cigarette used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>|
| Experimental: Product use sequence DECAB<br>Subjects use Product D on Day 1, Product E on Day 2, Product C on Day 3 and Product A on Day 4 and Product B on Day 5. | Other: Pulze device with heated tobacco sticks (Product A)<br>* Product A, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with heated tobacco sticks (Product B)<br>* Product B, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with nicotine-infused heated herbal sticks (Product C)<br>* Product C, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with nicotine-infused heated herbal sticks (Product D)<br>* Product D, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Conventional Cigarette (Product E)<br>* Subject's own brand combustible cigarette used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>|
| Experimental: Product use sequence EADBC<br>Subjects use Product E on Day 1, Product A on Day 2, Product D on Day 3 and Product B on Day 4 and Product C on Day 5. | Other: Pulze device with heated tobacco sticks (Product A)<br>* Product A, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with heated tobacco sticks (Product B)<br>* Product B, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with nicotine-infused heated herbal sticks (Product C)<br>* Product C, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Pulze device with nicotine-infused heated herbal sticks (Product D)<br>* Product D, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>Other: Conventional Cigarette (Product E)<br>* Subject's own brand combustible cigarette used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration), followed by an ad-libitum, 4-hour product use session on the same day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine Cmax | Maximum measured plasma nicotine concentration, for the controlled product use session | 5 minutes pre-study product use and at 2, 4, 6, 8, 10, 15, 30, 45, 60, 120, and 240 minutes following the start of study product use | 
| Nicotine AUCt | The area under the concentration time curve for nicotine, from time 0 to the last observed non-zero concentration, for the controlled product use session | 5 minutes pre-study product use and at 2, 4, 6, 8, 10, 15, 30, 45, 60, 120, and 240 minutes following the start of study product use | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking urges Emax | The maximum change from baseline Visual Analog Scale (VAS) score (VASpre-use - VASpost-use). Subjects answer the question Right now, how much would you like to smoke a cigarette? on a VAS: from Not at all on the left (0%) to A great deal on the right (100%), for the controlled product use session. | 10 minutes prior to the start of the product use session, and at 4, 8, 15, 45, 60, 120 and 240 following the start of study product use minutes | 
| Puff count | Number of puffs taken during 2 hours of the 4-hour ad-libitum product use session | 2 hours |