Healthy Volunteers
Conditions
Brief summary
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.
Interventions
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Cmax | 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 | Maximum observed plasma nicotine concentration |
| Nicotine AUCt | 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 | The area under the concentration-time curve for nicotine, from time 0 to the time of the last sampling timepoint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Orally Extracted of Nicotine | 20 minutes | The percentage of orally extracted nicotine from each pouch after 20 minutes of product use is calculated by subtracting the amount of nicotine left in the study pouches after use, to the amount of nicotine in unused reference pouches. Extracted dose of nicotine was assessed by the formula: (A\*B)/C - D where A = Reference value of nicotine as assessed by the average of extracted nicotine in unused reference pouches B = Weight of the unused pouch C = Reference weight value as assessed by the average of weight for unused reference pouches D = Extracted nicotine of the used pouch |
| Urge to Use Emax | 5 minutes prior to product use and at 5, 10, 15, 20, 25, 30, 45 minutes, and 1, 1.5, 2, 4, 6 and 8 hours post start of product use | 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). |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Product Sequence ABCD Subjects use Product A on Day 1, Product B on Day 2, Product C on Day 3 and Product D on Day 4
Product A: Tobacco-free pouch, 14 mg nicotine/pouch, used for 20 minutes
Product B: Tobacco-free pouch, 16 mg nicotine/pouch, used for 20 minutes
Product C: Tobacco-free pouch, 20 mg nicotine/pouch, used for 20 minutes
Product D: Tobacco pouch, 16.6 mg nicotine/pouch, used for 20 minutes | 7 |
| Product Sequence BCDA Subjects use Product B on Day 1, Product C on Day 2, Product D on Day 3 and Product A on Day 4
Product A: Tobacco-free pouch, 14 mg nicotine/pouch, used for 20 minutes
Product B: Tobacco-free pouch, 16 mg nicotine/pouch, used for 20 minutes
Product C: Tobacco-free pouch, 20 mg nicotine/pouch, used for 20 minutes
Product D: Tobacco pouch, 16.6 mg nicotine/pouch, used for 20 minutes | 7 |
| Product Sequence CDAB Subjects use Product C on Day 1, Product D on Day 2, Product A on Day 3 and Product B on Day 4
Product A: Tobacco-free pouch, 14 mg nicotine/pouch, used for 20 minutes
Product B: Tobacco-free pouch, 16 mg nicotine/pouch, used for 20 minutes
Product C: Tobacco-free pouch, 20 mg nicotine/pouch, used for 20 minutes
Product D: Tobacco pouch, 16.6 mg nicotine/pouch, used for 20 minutes | 7 |
| Product Sequence DABC Subjects use Product D on Day 1, Product A on Day 2, Product B on Day 3 and Product C on Day 4
Product A: Tobacco-free pouch, 14 mg nicotine/pouch, used for 20 minutes
Product B: Tobacco-free pouch, 16 mg nicotine/pouch, used for 20 minutes
Product C: Tobacco-free pouch, 20 mg nicotine/pouch, used for 20 minutes
Product D: Tobacco pouch, 16.6 mg nicotine/pouch, used for 20 minutes | 6 |
| Total | 27 |
Baseline characteristics
| Characteristic | Product Sequence ABCD | Product Sequence BCDA | Product Sequence CDAB | Product Sequence DABC | Total |
|---|---|---|---|---|---|
| Age, Continuous | 29.4 years STANDARD_DEVIATION 10.2 | 32.4 years STANDARD_DEVIATION 14.4 | 30.1 years STANDARD_DEVIATION 10 | 32.5 years STANDARD_DEVIATION 15 | 31.1 years STANDARD_DEVIATION 11.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 7 Participants | 7 Participants | 6 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 5 Participants | 6 Participants | 22 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 4 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants | 4 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 2 / 27 | 6 / 27 | 1 / 27 | 3 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 27 |
Outcome results
Primary
Nicotine AUCt
The area under the concentration-time curve for nicotine, from time 0 to the time of the last sampling timepoint
Time frame: 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
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 | 36.48 h*ng/mL | Standard Deviation 12.72 |
| Product B | Nicotine AUCt | 31.72 h*ng/mL | Standard Deviation 9.5 |
| Product C | Nicotine AUCt | 48.44 h*ng/mL | Standard Deviation 19.68 |
| Product D | Nicotine AUCt | 32.11 h*ng/mL | Standard Deviation 9.46 |
Primary
Nicotine Cmax
Maximum observed plasma nicotine concentration
Time frame: 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
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 | 14.98 ng/mL | Standard Deviation 4.96 |
| Product B | Nicotine Cmax | 13.43 ng/mL | Standard Deviation 4.97 |
| Product C | Nicotine Cmax | 19.35 ng/mL | Standard Deviation 6.58 |
| Product D | Nicotine Cmax | 13.85 ng/mL | Standard Deviation 3.85 |
Secondary
Orally Extracted Amount of Nicotine
Orally extracted fraction of nicotine (%) in the pouch after the 20-minute use period.
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Orally Extracted Amount of Nicotine | 19.10 Percentage of nicotine | Standard Deviation 9.98 |
| Product B | Orally Extracted Amount of Nicotine | 22.9 Percentage of nicotine | Standard Deviation 10.3 |
| Product C | Orally Extracted Amount of Nicotine | 21.9 Percentage of nicotine | Standard Deviation 9.77 |
| Product D | Orally Extracted Amount of Nicotine | 14.0 Percentage of nicotine | Standard Deviation 4.63 |
Secondary
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).
Time frame: 5 minutes prior to product use and at 5, 10, 15, 20, 25, 30, 45 minutes, and 1, 1.5, 2, 4, 6 and 8 hours post start of product use
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 | Urge to Use Emax | 61.7 mm | Standard Deviation 23.3 |
| Product B | Urge to Use Emax | 57.7 mm | Standard Deviation 19.7 |
| Product C | Urge to Use Emax | 66.1 mm | Standard Deviation 22.4 |
| Product D | Urge to Use Emax | 52.7 mm | Standard Deviation 25.7 |