Healthy Volunteers
Conditions
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.
Interventions
OTHERA
Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes
OTHERB
Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes
OTHERC
Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes
OTHERD
Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes
OTHERE
Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes
Sponsors
Imperial Brands PLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 99 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Extraction | 20 minutes | Extraction fraction (%) of nicotine in used product pouches after 20 minutes of use. |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
A: Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes
B: Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes
C: Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes
D: Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes
E: Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes | 5 |
| BCDEA Same as previous arm but in a different randomization order.
A: Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes
B: Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes
C: Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes
D: Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes
E: Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes | 5 |
| CDEAB Same as previous arm but in a different randomization order.
A: Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes
B: Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes
C: Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes
D: Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes
E: Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes | 5 |
| DEABC Same as previous arm but in a different randomization order.
A: Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes
B: Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes
C: Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes
D: Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes
E: Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes | 5 |
| EABCD Same as previous arm but in a different randomization order.
A: Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes
B: Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes
C: Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes
D: Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes
E: Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes | 4 |
| Total | 24 |
Baseline characteristics
| Characteristic | ABCDE | BCDEA | CDEAB | DEABC | EABCD | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 23.2 years STANDARD_DEVIATION 4.3 | 25.0 years STANDARD_DEVIATION 1.4 | 32.6 years STANDARD_DEVIATION 10.8 | 34.2 years STANDARD_DEVIATION 10 | 38.5 years STANDARD_DEVIATION 14.2 | 30.4 years STANDARD_DEVIATION 10 |
| Body Mass Index (BMI) | 25.7 kg/m^2 STANDARD_DEVIATION 4.4 | 21.2 kg/m^2 STANDARD_DEVIATION 2.1 | 24.6 kg/m^2 STANDARD_DEVIATION 3.6 | 24.5 kg/m^2 STANDARD_DEVIATION 2.1 | 25.1 kg/m^2 STANDARD_DEVIATION 4.8 | 24.2 kg/m^2 STANDARD_DEVIATION 3.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 5 Participants | 4 Participants | 4 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 5 Participants | 4 Participants | 2 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 23 | 0 / 22 | 0 / 23 | 0 / 22 |
| other Total, other adverse events | 3 / 22 | 0 / 23 | 1 / 22 | 1 / 23 | 3 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 23 | 0 / 22 | 0 / 23 | 0 / 22 |
Outcome results
Primary
Nicotine AUCt
Area under the plasma nicotine concentration-time curve at the last timepoint measured (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
Population: The analysis population represents all subjects who used a specific product. The overall number of participants analyzed for each product is therefore different from the number of participants in each arm provided in the Participant Flow module.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Nicotine AUCt | 12.23 h*ng/mL | Standard Deviation 4.996 |
| Product B | Nicotine AUCt | 18.35 h*ng/mL | Standard Deviation 8.18 |
| Product C | Nicotine AUCt | 21.13 h*ng/mL | Standard Deviation 11.38 |
| Product D | Nicotine AUCt | 31.31 h*ng/mL | Standard Deviation 13.98 |
| Product E | Nicotine AUCt | 19.60 h*ng/mL | Standard Deviation 10.75 |
Primary
Nicotine Cmax
Maximum plasma concentration of 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
Population: The analysis population represents all subjects who used a specific product. The overall number of participants analyzed for each product is therefore different from the number of participants in each arm provided in the Participant Flow module.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Nicotine Cmax | 5.154 ng/mL | Standard Deviation 1.662 |
| Product B | Nicotine Cmax | 7.856 ng/mL | Standard Deviation 2.451 |
| Product C | Nicotine Cmax | 9.553 ng/mL | Standard Deviation 4.083 |
| Product D | Nicotine Cmax | 12.51 ng/mL | Standard Deviation 4.377 |
| Product E | Nicotine Cmax | 11.60 ng/mL | Standard Deviation 5.171 |
Secondary
Nicotine Extraction
Extraction fraction (%) of nicotine in used product pouches after 20 minutes of use.
Time frame: 20 minutes
Population: The analysis population represents all subjects who used a specific product. The overall number of participants analyzed for each product is therefore different from the number of participants in each arm provided in the Participant Flow module.~Only analyzed for pouch products (A, B, C and D), not for Product E (conventional cigarette).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Nicotine Extraction | 13.47 Percent of nicotine used | Standard Deviation 5.321 |
| Product B | Nicotine Extraction | 14.31 Percent of nicotine used | Standard Deviation 8.181 |
| Product C | Nicotine Extraction | 12.56 Percent of nicotine used | Standard Deviation 5.01 |
| Product D | Nicotine Extraction | 18.61 Percent of nicotine used | Standard Deviation 8.608 |