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

Not Applicable

Completed

Conditions: Healthy Volunteers

Interventions: Other: A
Other: B
Other: C
Other: D
Other: E

Registration Number: NCT04891406

Lead Sponsor: Imperial Brands PLC

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
DEABC	C	Same as previous arm but in a different randomization order.
EABCD	D	Same as previous arm but in a different randomization order.
ABCDE	B	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.
CDEAB	C	Same as previous arm but in a different randomization order.
EABCD	B	Same as previous arm but in a different randomization order.
BCDEA	B	Same as previous arm but in a different randomization order.
BCDEA	D	Same as previous arm but in a different randomization order.
ABCDE	A	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.
CDEAB	D	Same as previous arm but in a different randomization order.
DEABC	A	Same as previous arm but in a different randomization order.
ABCDE	E	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.
BCDEA	E	Same as previous arm but in a different randomization order.
CDEAB	E	Same as previous arm but in a different randomization order.
ABCDE	C	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.
ABCDE	D	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.
BCDEA	A	Same as previous arm but in a different randomization order.
DEABC	B	Same as previous arm but in a different randomization order.
DEABC	D	Same as previous arm but in a different randomization order.
DEABC	E	Same as previous arm but in a different randomization order.
BCDEA	C	Same as previous arm but in a different randomization order.
CDEAB	A	Same as previous arm but in a different randomization order.
CDEAB	B	Same as previous arm but in a different randomization order.
EABCD	A	Same as previous arm but in a different randomization order.
EABCD	C	Same as previous arm but in a different randomization order.
EABCD	E	Same as previous arm but in a different randomization order.

Primary Outcome Measures

Name	Time	Method
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	Maximum plasma concentration of nicotine (Cmax)
Nicotine 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	Area under the plasma nicotine concentration-time curve at the last timepoint measured (AUCt)

Secondary Outcome Measures