A Randomised, Cross-over, Relative Bioavailability Study of Nicotine Delivery and Nicotine Extraction From Oral Products

Study Overview
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Brief Summary
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This study is a randomised cross-over, open-label, confinement study conducted in 24 male or female snus and cigarette consumers. The study investigates 5 different nicotine containing products in a cross-over fashion. The study incorporates pharmacokinetics evaluation, nicotine extraction evaluation, subjective questionnaire assessments as well as safety evaluation. During the study participation, subjects come for two visits to the clinic, including a 5-day confinement period.

Official Title
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A Randomised, Cross-over, Relative Bioavailability Study of Nicotine Delivery and Nicotine Extraction From Oral Products (Traditional Snus, Conventional Cigarette and Three Oral Tobacco-free Nicotine Delivery Products)

Conditions
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Healthy Volunteers

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) ≥ 18.0 and ≤ 30.0 kg/m Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator Dual user of snus and conventional cigarettes for ≥1 year, with a minimum weekly consumption of two or more snus cans and >5 cigarettes, and who is willing and able to use brands with nicotine content ≥1% 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 Positive for HIV, hepatitis B or C After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges: Systolic blood pressure <90 or >140 mmHg, or Diastolic blood pressure <50 or >90 mmHg, or Pulse <40 or >90 bpm Alcohol or drug abuse Use, or history of use of anabolic steroids Allergy/hypersensitivity to drugs with a similar chemical structure or class to nicotine Excessive caffeine consumption (daily intake of >5 cups) Female subjects who are pregnant or breastfeeding

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 |
| --- | --- |
| Other: ABCDE<br>Subjects use product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes on Day 1, then switch to use product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 min on Day 2, then product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 min on Day 3, then D (nicotine pouch, 10.6 mg/pouch) on Day 4 and finally E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette), smoked in approximately 5 minutes with puffs taken at regular intervals approximately 30 seconds apart, on Day 5. Subjects can use their assigned product ad libitum on each study day, after all study assessments are performed, until 10pm. A washout period of product abstinence is observed between products, overnight. | Other: A<br>* Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes<br>* Other names: Product A;Other: B<br>* Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes<br>* Other names: Product B;Other: C<br>* Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes<br>* Other names: Product C;Other: D<br>* Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes<br>* Other names: Product D;Other: E<br>* Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes<br>* Other names: Product E;|
| Other: BCDEA<br>Same as previous arm but in a different randomization order. | Other: A<br>* Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes<br>* Other names: Product A;Other: B<br>* Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes<br>* Other names: Product B;Other: C<br>* Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes<br>* Other names: Product C;Other: D<br>* Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes<br>* Other names: Product D;Other: E<br>* Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes<br>* Other names: Product E;|
| Other: CDEAB<br>Same as previous arm but in a different randomization order. | Other: A<br>* Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes<br>* Other names: Product A;Other: B<br>* Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes<br>* Other names: Product B;Other: C<br>* Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes<br>* Other names: Product C;Other: D<br>* Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes<br>* Other names: Product D;Other: E<br>* Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes<br>* Other names: Product E;|
| Other: DEABC<br>Same as previous arm but in a different randomization order. | Other: A<br>* Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes<br>* Other names: Product A;Other: B<br>* Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes<br>* Other names: Product B;Other: C<br>* Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes<br>* Other names: Product C;Other: D<br>* Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes<br>* Other names: Product D;Other: E<br>* Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes<br>* Other names: Product E;|
| Other: EABCD<br>Same as previous arm but in a different randomization order. | Other: A<br>* Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes<br>* Other names: Product A;Other: B<br>* Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes<br>* Other names: Product B;Other: C<br>* Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes<br>* Other names: Product C;Other: D<br>* Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes<br>* Other names: Product D;Other: E<br>* Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes<br>* Other names: Product E;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine Cmax | Maximum plasma concentration of nicotine (Cmax) | Pre-use and at 2, 5, 7, 15, 20, 30, 45, 60, 90 minutes, and 2, 4, 6 and 8 hours post use start | 
| Nicotine AUCt | Area under the plasma nicotine concentration-time curve at the last timepoint measured (AUCt) | Pre-use and at 2, 5, 7, 15, 20, 30, 45, 60, 90 minutes, and 2, 4, 6 and 8 hours post use start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine Extraction | Extraction fraction (%) of nicotine in used product pouches after 20 minutes of use. | 20 minutes |