Trial Outcomes & Findings for A Randomised, Cross-over, Relative Bioavailability Study of Nicotine Delivery and Nicotine Extraction From Oral Products (NCT NCT04891406)

Results Overview

Maximum plasma concentration of nicotine (Cmax)

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

24 participants

Primary outcome timeframe

Pre-use and at 2, 5, 7, 15, 20, 30, 45, 60, 90 minutes, and 2, 4, 6 and 8 hours post use start

Results posted on

2023-10-13

Participant Flow

Participant milestones

Participant milestones
Measure	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	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	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	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	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
Overall Study STARTED	5	5	5	5	4
Overall Study COMPLETED	5	4	5	5	3
Overall Study NOT COMPLETED	0	1	0	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ABCDE n=5 Participants 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	BCDEA n=5 Participants 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	CDEAB n=5 Participants 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	DEABC n=5 Participants 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	EABCD n=4 Participants 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	Total n=24 Participants Total of all reporting groups
Age, Continuous	23.2 years STANDARD_DEVIATION 4.3 • n=5 Participants	25.0 years STANDARD_DEVIATION 1.4 • n=7 Participants	32.6 years STANDARD_DEVIATION 10.8 • n=5 Participants	34.2 years STANDARD_DEVIATION 10.0 • n=4 Participants	38.5 years STANDARD_DEVIATION 14.2 • n=21 Participants	30.4 years STANDARD_DEVIATION 10.0 • n=10 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	3 Participants n=10 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	2 Participants n=21 Participants	21 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	4 Participants n=21 Participants	22 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Body Mass Index (BMI)	25.7 kg/m^2 STANDARD_DEVIATION 4.4 • n=5 Participants	21.2 kg/m^2 STANDARD_DEVIATION 2.1 • n=7 Participants	24.6 kg/m^2 STANDARD_DEVIATION 3.6 • n=5 Participants	24.5 kg/m^2 STANDARD_DEVIATION 2.1 • n=4 Participants	25.1 kg/m^2 STANDARD_DEVIATION 4.8 • n=21 Participants	24.2 kg/m^2 STANDARD_DEVIATION 3.6 • n=10 Participants

PRIMARY outcome

Timeframe: 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.

Maximum plasma concentration of nicotine (Cmax)

Outcome measures

Outcome measures
Measure	Product A n=21 Participants Subjects who used product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes	Product B n=22 Participants Subjects who used product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 min	Product C n=22 Participants Subjects who used product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 min	Product D n=23 Participants Subjects who used Product D (nicotine pouch, 10.6 mg/pouch) for 20 min	Product E n=22 Participants Subjects who used Product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette), smoked in approximately 5 minutes
Nicotine Cmax	5.154 ng/mL Standard Deviation 1.662	7.856 ng/mL Standard Deviation 2.451	9.553 ng/mL Standard Deviation 4.083	12.51 ng/mL Standard Deviation 4.377	11.60 ng/mL Standard Deviation 5.171

PRIMARY outcome

Timeframe: 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.

Area under the plasma nicotine concentration-time curve at the last timepoint measured (AUCt)

Outcome measures

Outcome measures
Measure	Product A n=21 Participants Subjects who used product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes	Product B n=22 Participants Subjects who used product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 min	Product C n=22 Participants Subjects who used product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 min	Product D n=23 Participants Subjects who used Product D (nicotine pouch, 10.6 mg/pouch) for 20 min	Product E n=22 Participants Subjects who used Product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette), smoked in approximately 5 minutes
Nicotine AUCt	12.23 h*ng/mL Standard Deviation 4.996	18.35 h*ng/mL Standard Deviation 8.180	21.13 h*ng/mL Standard Deviation 11.38	31.31 h*ng/mL Standard Deviation 13.98	19.60 h*ng/mL Standard Deviation 10.75

SECONDARY outcome

Timeframe: 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).

Extraction fraction (%) of nicotine in used product pouches after 20 minutes of use.