Trial Outcomes & Findings for A Randomised, Cross-Over, Nicotine Pharmacokinetic and Pharmacodynamic Study of Heated Tobacco Products Compared to Combustible Cigarettes (NCT NCT05459857)

NCT ID: NCT05459857

Last Updated: 2025-02-03

Results Overview

Maximum measured plasma nicotine concentration, baseline-adjusted

Recruitment status

COMPLETED

Study phase

Target enrollment

24 participants

Primary outcome timeframe

5 minutes pre-study product use and at 2, 4, 6, 8, 10, 15, 30, 45, 60, 120, and 240 minutes following the start of study product use

Results posted on

2025-02-03

Participant Flow

Participant milestones

Participant milestones
Measure	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: Heated tobacco (HT) device with Intense HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product B: Heated tobacco (HT) device with Regular HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product C: Heated tobacco (HT) device with Menthol HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product D: Subject's own brand combustible cigarette, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product Sequence BDAC Subjects use Product B on Day 1, Product D on Day 2, Product A on Day 3 and Product C on Day 4 Product A: Heated tobacco (HT) device with Intense HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product B: Heated tobacco (HT) device with Regular HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product C: Heated tobacco (HT) device with Menthol HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product D: Subject's own brand combustible cigarette, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product Sequence CADB Subjects use Product C on Day 1, Product A on Day 2, Product D on Day 3 and Product B on Day 4 Product A: Heated tobacco (HT) device with Intense HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product B: Heated tobacco (HT) device with Regular HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product C: Heated tobacco (HT) device with Menthol HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product D: Subject's own brand combustible cigarette, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product Sequence DCBA Subjects use Product D on Day 1, Product C on Day 2, Product B on Day 3 and Product A on Day 4 Product A: Heated tobacco (HT) device with Intense HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product B: Heated tobacco (HT) device with Regular HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product C: Heated tobacco (HT) device with Menthol HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product D: Subject's own brand combustible cigarette, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)
Overall Study STARTED	6	6	6	6
Overall Study COMPLETED	5	6	6	6
Overall Study NOT COMPLETED	1	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Randomised, Cross-Over, Nicotine Pharmacokinetic and Pharmacodynamic Study of Heated Tobacco Products Compared to Combustible Cigarettes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Product Sequence ABCD n=6 Participants 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: Heated tobacco (HT) device with Intense HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product B: Heated tobacco (HT) device with Regular HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product C: Heated tobacco (HT) device with Menthol HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product D: Subject's own brand combustible cigarette, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product Sequence BDAC n=6 Participants Subjects use Product B on Day 1, Product D on Day 2, Product A on Day 3 and Product C on Day 4 Product A: Heated tobacco (HT) device with Intense HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product B: Heated tobacco (HT) device with Regular HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product C: Heated tobacco (HT) device with Menthol HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product D: Subject's own brand combustible cigarette, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product Sequence CADB n=6 Participants Subjects use Product C on Day 1, Product A on Day 2, Product D on Day 3 and Product B on Day 4 Product A: Heated tobacco (HT) device with Intense HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product B: Heated tobacco (HT) device with Regular HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product C: Heated tobacco (HT) device with Menthol HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product D: Subject's own brand combustible cigarette, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product Sequence DCBA n=6 Participants Subjects use Product D on Day 1, Product C on Day 2, Product B on Day 3 and Product A on Day 4 Product A: Heated tobacco (HT) device with Intense HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product B: Heated tobacco (HT) device with Regular HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product C: Heated tobacco (HT) device with Menthol HT sticks, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration) Product D: Subject's own brand combustible cigarette, used under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Total n=24 Participants Total of all reporting groups
Age, Continuous	40.7 years STANDARD_DEVIATION 12.75 • n=5 Participants	31.8 years STANDARD_DEVIATION 8.11 • n=7 Participants	49.2 years STANDARD_DEVIATION 7.14 • n=5 Participants	42.2 years STANDARD_DEVIATION 12.5 • n=4 Participants	41.0 years STANDARD_DEVIATION 11.59 • n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	10 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	14 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	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
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	24 Participants n=21 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
Race (NIH/OMB) American Indian or Alaska Native	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
Race (NIH/OMB) Asian	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
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	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
Race (NIH/OMB) Black or African American	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
Race (NIH/OMB) White	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	24 Participants n=21 Participants
Race (NIH/OMB) More than one race	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
Race (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

PRIMARY outcome

Timeframe: 5 minutes pre-study product use and at 2, 4, 6, 8, 10, 15, 30, 45, 60, 120, and 240 minutes following the start of study 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.

Maximum measured plasma nicotine concentration, baseline-adjusted

Outcome measures

Outcome measures
Measure	Product A n=23 Participants Subjects using Product A (Heated Tobacco device with Intense sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product B n=24 Participants Subjects using Product B (Heated tobacco device with Regular sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product C n=24 Participants Subjects using Product C (Heated tobacco device with menthol sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product D n=23 Participants Subjects using Product D (subject's own brand combustible cigarette) for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)
Nicotine Cmax	10.500 ng/mL Standard Deviation 8.284	7.539 ng/mL Standard Deviation 4.653	8.191 ng/mL Standard Deviation 4.447	21.680 ng/mL Standard Deviation 10.810

PRIMARY outcome

Timeframe: 5 minutes pre-study product use and at 2, 4, 6, 8, 10, 15, 30, 45, 60, 120, and 240 minutes following the start of study product use

The area under the concentration time curve for nicotine, from time 0 to the last observed non-zero concentration, baseline-adjusted

Outcome measures

Outcome measures
Measure	Product A n=23 Participants Subjects using Product A (Heated Tobacco device with Intense sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product B n=24 Participants Subjects using Product B (Heated tobacco device with Regular sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product C n=24 Participants Subjects using Product C (Heated tobacco device with menthol sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product D n=23 Participants Subjects using Product D (subject's own brand combustible cigarette) for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)
Nicotine AUCt	746.00 ng*min/mL Standard Deviation 271.24	586.50 ng*min/mL Standard Deviation 192.03	585.00 ng*min/mL Standard Deviation 191.16	1514.00 ng*min/mL Standard Deviation 368.91

SECONDARY outcome

Timeframe: 10 minutes prior to the start of the product use session

The subjects self-assess their urge to smoke by answering the question: "How strong is your current urge to smoke your usual brand cigarette?" on a Visual Analog Scale (VAS), with scores of 0 to 100, with 0 being 'not at all' and 100 being 'extreme'.

Outcome measures

Outcome measures
Measure	Product A n=23 Participants Subjects using Product A (Heated Tobacco device with Intense sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product B n=23 Participants Subjects using Product B (Heated tobacco device with Regular sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product C n=24 Participants Subjects using Product C (Heated tobacco device with menthol sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product D n=22 Participants Subjects using Product D (subject's own brand combustible cigarette) for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)
Urge to Smoke Pre-Use	63.8 Units on a scale Standard Deviation 27.4	57.8 Units on a scale Standard Deviation 30.9	64.2 Units on a scale Standard Deviation 29.6	62.8 Units on a scale Standard Deviation 30.1

SECONDARY outcome

Timeframe: At 240 min following the start of study product use

Outcome measures

Outcome measures
Measure	Product A n=24 Participants Subjects using Product A (Heated Tobacco device with Intense sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product B n=24 Participants Subjects using Product B (Heated tobacco device with Regular sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product C n=24 Participants Subjects using Product C (Heated tobacco device with menthol sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product D n=23 Participants Subjects using Product D (subject's own brand combustible cigarette) for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)
Urge to Smoke Post-Use	61.4 units on a scale Standard Deviation 28.4	67.5 units on a scale Standard Deviation 26.3	71.3 units on a scale Standard Deviation 21.7	67.5 units on a scale Standard Deviation 24.8

SECONDARY outcome

Timeframe: 10 minutes prior to the start of the product use session, and at 4, 8, 15, 45, 60, 210 and 240 minutes following the start of study product use

The subjects self-assess their urge to smoke at defined time points by answering the question: "How strong is your current urge to smoke your usual brand cigarette?" on a Visual Analog Scale (VAS), with scores of 0 to 100, with 0 being 'not at all' and 100 being 'extreme'. Emax is calculated as the maximum absolute value of change from baseline (i.e., the maximum response) in VAS scores.

Outcome measures

Outcome measures
Measure	Product A n=23 Participants Subjects using Product A (Heated Tobacco device with Intense sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product B n=23 Participants Subjects using Product B (Heated tobacco device with Regular sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product C n=24 Participants Subjects using Product C (Heated tobacco device with menthol sticks), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product D n=22 Participants Subjects using Product D (subject's own brand combustible cigarette) for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)
Smoking Urges Emax	40.30 units on a scale Standard Deviation 25.75	32.90 units on a scale Standard Deviation 27.13	39.70 units on a scale Standard Deviation 29.72	49.80 units on a scale Standard Deviation 30.10

Adverse Events

Product A

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Product B

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Product C

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Product D

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Product A n=24 participants at risk Subjects using Product A (Heated Tobacco device Intense), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product B n=24 participants at risk Subjects using Product B (Heated tobacco device Regular), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product C n=24 participants at risk Subjects using Product C (Heated tobacco device menthol), for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)	Product D n=23 participants at risk Subjects using Product D (subject's own brand combustible cigarette) for one product use session, under controlled conditions (i.e., completely use a single unit of the product, with puffs taken at 30-second intervals and puffs 3 seconds in duration)
Gastrointestinal disorders Constipation	0.00% 0/24 • From screening until follow-up (7 days after the final product use)	4.2% 1/24 • From screening until follow-up (7 days after the final product use)	0.00% 0/24 • From screening until follow-up (7 days after the final product use)	0.00% 0/23 • From screening until follow-up (7 days after the final product use)
General disorders Catheter site pain	8.3% 2/24 • From screening until follow-up (7 days after the final product use)	0.00% 0/24 • From screening until follow-up (7 days after the final product use)	4.2% 1/24 • From screening until follow-up (7 days after the final product use)	0.00% 0/23 • From screening until follow-up (7 days after the final product use)
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/24 • From screening until follow-up (7 days after the final product use)	4.2% 1/24 • From screening until follow-up (7 days after the final product use)	0.00% 0/24 • From screening until follow-up (7 days after the final product use)	0.00% 0/23 • From screening until follow-up (7 days after the final product use)
Nervous system disorders Dizziness	0.00% 0/24 • From screening until follow-up (7 days after the final product use)	4.2% 1/24 • From screening until follow-up (7 days after the final product use)	0.00% 0/24 • From screening until follow-up (7 days after the final product use)	0.00% 0/23 • From screening until follow-up (7 days after the final product use)

Additional Information

Libby Clarke

Imperial Brands PLC

Phone: +44 (0117) 3320221

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place