A Relative Bioavailability Study of Nicotine Delivery From Selected Oral Nicotine Products

Study Overview
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Brief Summary
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This will be a randomised, cross-over, single-blind, confinement study conducted in 27 male or female snus or nicotine pouch users. The study will investigate 4 different nicotine containing products in a cross-over design, incorporating pharmacokinetic (PK) evaluation, nicotine extraction evaluation, subjective questionnaire assessments as well as safety and tolerability evaluation. During the study participation, subjects will come for 2 visits to the clinic, including a screening visit and a 4-day confinement period. A final follow up end-of-study telephone call will be performed within a week of last product use.

Official Title
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A Randomised, Cross-over, Single-blind, Relative Bioavailability Study of Nicotine Delivery From Selected Oral Nicotine Products

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Other: Product A
* Other: Product B
* Other: Product C
* Other: Product D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI ≥ 18.0 and ≤ 30.0 kg/m2 Clinically normal medical history User of snus or nicotine pouches for ≥1 year, with a minimum weekly use of 2 or more snus or nicotine pouch cans and who is willing and considered able to use brands with nicotine content in the range of 14 to 20 mg nicotine/pouch Exclusion Criteria: History of any clinically significant disease or disorder Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first use of IP. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and HIV Female subjects who are pregnant or breastfeeding Presence or history of drug or alcohol abuse Excessive caffeine consumption defined by a daily intake of >5 cups of caffeine containing beverages Intend to change nicotine-use habit or make a quit attempt within the next 3 months from the screening visit.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 99 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: Product A<br>* Tobacco-free pouch, 14 mg nicotine/pouch, used for 20 minutes<br>Other: Product B<br>* Tobacco-free pouch, 16 mg nicotine/pouch, used for 20 minutes<br>Other: Product C<br>* Tobacco-free pouch, 20 mg nicotine/pouch, used for 20 minutes<br>Other: Product D<br>* Tobacco pouch, 16.6 mg nicotine/pouch, used for 20 minutes<br>|
| Experimental: Product sequence BCDA<br>Subjects use Product B on Day 1, Product C on Day 2, Product D on Day 3 and Product A on Day 4 | Other: Product A<br>* Tobacco-free pouch, 14 mg nicotine/pouch, used for 20 minutes<br>Other: Product B<br>* Tobacco-free pouch, 16 mg nicotine/pouch, used for 20 minutes<br>Other: Product C<br>* Tobacco-free pouch, 20 mg nicotine/pouch, used for 20 minutes<br>Other: Product D<br>* Tobacco pouch, 16.6 mg nicotine/pouch, used for 20 minutes<br>|
| Experimental: Product sequence CDAB<br>Subjects use Product C on Day 1, Product D on Day 2, Product A on Day 3 and Product B on Day 4 | Other: Product A<br>* Tobacco-free pouch, 14 mg nicotine/pouch, used for 20 minutes<br>Other: Product B<br>* Tobacco-free pouch, 16 mg nicotine/pouch, used for 20 minutes<br>Other: Product C<br>* Tobacco-free pouch, 20 mg nicotine/pouch, used for 20 minutes<br>Other: Product D<br>* Tobacco pouch, 16.6 mg nicotine/pouch, used for 20 minutes<br>|
| Experimental: Product sequence DABC<br>Subjects use Product D on Day 1, Product A on Day 2, Product B on Day 3 and Product C on Day 4 | Other: Product A<br>* Tobacco-free pouch, 14 mg nicotine/pouch, used for 20 minutes<br>Other: Product B<br>* Tobacco-free pouch, 16 mg nicotine/pouch, used for 20 minutes<br>Other: Product C<br>* Tobacco-free pouch, 20 mg nicotine/pouch, used for 20 minutes<br>Other: Product D<br>* Tobacco pouch, 16.6 mg nicotine/pouch, used for 20 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine Cmax | Maximum observed plasma nicotine concentration | 5 minutes prior to product use and 5, 10, 15, 20, 25, 30, 45, 60, 90 minutes, 2, 4, 6 and 8 hours post start of product use | 
| Nicotine AUCt | The area under the concentration-time curve for nicotine, from time 0 to the time of the last sampling timepoint | 5 minutes prior to product use and at 5, 10, 15, 20, 25, 30, 45, 60, 90 minutes, 2, 4, 6 and 8 hours post start of product use | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extracted dose of nicotine | Extraction fraction (%) of nicotine in the pouch after the 20-minute use period. | 20 minutes | 
| Urge to use Emax | The subjects will self-assess their urge to use a nicotine pouch, pre-use and after use, by answering the question: How strong is your urge to use a nicotine pouch right now? on a 100 mm visual analogue scale (VAS), with the anchor points 0 mm (= not at all/no urge) and 100 mm (= extremely/extreme urge). Emax is the maximum change from baseline VAS score (VASpre-use - VASpost-use). | 5 minutes prior to product use and at 5, 10, 15, 20, 25, 30, 45, 60, 90 minutes, 2, 4, 6 and 8 hours post start of product use |