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)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Imperial Brands PLC
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Nicotine Cmax
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 19 Years to 99 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
CDEAB
Same as previous arm but in a different randomization order.
Intervention: B (Other)
ABCDE
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.
Intervention: A (Other)
ABCDE
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.
Intervention: B (Other)
ABCDE
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.
Intervention: E (Other)
BCDEA
Same as previous arm but in a different randomization order.
Intervention: A (Other)
BCDEA
Same as previous arm but in a different randomization order.
Intervention: B (Other)
BCDEA
Same as previous arm but in a different randomization order.
Intervention: E (Other)
CDEAB
Same as previous arm but in a different randomization order.
Intervention: A (Other)
CDEAB
Same as previous arm but in a different randomization order.
Intervention: E (Other)
DEABC
Same as previous arm but in a different randomization order.
Intervention: A (Other)
DEABC
Same as previous arm but in a different randomization order.
Intervention: B (Other)
DEABC
Same as previous arm but in a different randomization order.
Intervention: E (Other)
EABCD
Same as previous arm but in a different randomization order.
Intervention: A (Other)
EABCD
Same as previous arm but in a different randomization order.
Intervention: B (Other)
EABCD
Same as previous arm but in a different randomization order.
Intervention: E (Other)
CDEAB
Same as previous arm but in a different randomization order.
Intervention: C (Other)
EABCD
Same as previous arm but in a different randomization order.
Intervention: D (Other)
EABCD
Same as previous arm but in a different randomization order.
Intervention: C (Other)
DEABC
Same as previous arm but in a different randomization order.
Intervention: D (Other)
DEABC
Same as previous arm but in a different randomization order.
Intervention: C (Other)
CDEAB
Same as previous arm but in a different randomization order.
Intervention: D (Other)
BCDEA
Same as previous arm but in a different randomization order.
Intervention: D (Other)
BCDEA
Same as previous arm but in a different randomization order.
Intervention: C (Other)
ABCDE
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.
Intervention: D (Other)
ABCDE
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.
Intervention: C (Other)
Outcomes
Primary Outcomes
Nicotine Cmax
Time Frame: Pre-use and at 2, 5, 7, 15, 20, 30, 45, 60, 90 minutes, and 2, 4, 6 and 8 hours post use start
Maximum plasma concentration of nicotine (Cmax)
Nicotine AUCt
Time Frame: Pre-use and at 2, 5, 7, 15, 20, 30, 45, 60, 90 minutes, and 2, 4, 6 and 8 hours post use start
Area under the plasma nicotine concentration-time curve at the last timepoint measured (AUCt)
Secondary Outcomes
- Nicotine Extraction(20 minutes)