A Randomised, Cross-Over, Nicotine Pharmacokinetic and Pharmacodynamic Study of Heated Tobacco Products Compared to Combustible Cigarettes

Study Overview
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Brief Summary
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This is a randomised, cross-over, open-label, confinement study conducted in 24 adult male or female smokers of combustible cigarettes. The study investigates combustible and heated tobacco (HT) products in a cross-over design, including pharmacokinetic evaluation, subjective questionnaire assessments, as well as safety evaluation. Subjects will perform a screening visit and a 5-day confinement period.

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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Other: Heated tobacco device Intense (Product A)
* Other: Heated tobacco device Regular (Product B)
* Other: Heated tobacco device Menthol (Product C)
* Other: Combustible cigarette (Product D)


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 A female subject of childbearing potential must use contraception Male subject 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 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 sequence ABCD<br>Subjects use Product A on Day 1, Product B on Day 2, Product C on Day 3 and Product D on Day 4 | Other: Heated tobacco device Intense (Product A)<br>* Heated Tobacco device Intense, 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)<br>Other: Heated tobacco device Regular (Product B)<br>* Heated Tobacco device Regular, 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)<br>Other: Heated tobacco device Menthol (Product C)<br>* Heated Tobacco device Menthol, 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)<br>Other: Combustible cigarette (Product D)<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)<br>|
| Experimental: Product sequence BDAC<br>Subjects use Product B on Day 1, Product D on Day 2, Product A on Day 3 and Product C on Day 4 | Other: Heated tobacco device Intense (Product A)<br>* Heated Tobacco device Intense, 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)<br>Other: Heated tobacco device Regular (Product B)<br>* Heated Tobacco device Regular, 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)<br>Other: Heated tobacco device Menthol (Product C)<br>* Heated Tobacco device Menthol, 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)<br>Other: Combustible cigarette (Product D)<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)<br>|
| Experimental: Product sequence CADB<br>Subjects use Product C on Day 1, Product A on Day 2, Product D on Day 3 and Product B on Day 4 | Other: Heated tobacco device Intense (Product A)<br>* Heated Tobacco device Intense, 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)<br>Other: Heated tobacco device Regular (Product B)<br>* Heated Tobacco device Regular, 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)<br>Other: Heated tobacco device Menthol (Product C)<br>* Heated Tobacco device Menthol, 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)<br>Other: Combustible cigarette (Product D)<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)<br>|
| Experimental: Product sequence DCBA<br>Subjects use Product D on Day 1, Product C on Day 2, Product B on Day 3 and Product A on Day 4 | Other: Heated tobacco device Intense (Product A)<br>* Heated Tobacco device Intense, 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)<br>Other: Heated tobacco device Regular (Product B)<br>* Heated Tobacco device Regular, 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)<br>Other: Heated tobacco device Menthol (Product C)<br>* Heated Tobacco device Menthol, 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)<br>Other: Combustible cigarette (Product D)<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)<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 | 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 | 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 How strong is your urge to smoke right now? on a VAS: from Not at all on the left (0%) to Extreme on the right (100%). | 10 minutes prior to the start of the product use session, and at 4, 8, 15, 45, 60, 210 and 240 following the start of study product use minutes |