Healthy Volunteers
Conditions
Brief summary
This is a randomised, cross-over, open-label, confinement study conducted in 24 adult male or female smokers of combustible cigarettes. The study investigates combustible and heated tobacco (HT) products in a cross-over design, including pharmacokinetic evaluation, subjective questionnaire assessments, as well as safety evaluation. Subjects will perform a screening visit and a 5-day confinement period.
Interventions
OTHERProduct 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)
OTHERProduct 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)
OTHERProduct 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)
OTHERProduct 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)
Sponsors
Imperial Brands PLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Reports smoking an average of at least 10 manufactured combustible (menthol or non-menthol) cigarettes per day for at least 12 months prior to Screening * Has a positive urine cotinine (\>500 ng/mL) at Screening * Has an exhaled carbon monoxide \>10 ppm at Screening * A female subject of childbearing potential must use contraception * Male subject must use contraception
Exclusion criteria
* Has a history or presence of clinically significant disease or condition that, in the opinion of the Investigator, would jeopardise the safety of the subject or impact the validity of the study results. * Has a positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) at Screening * Has a fever (\>38.05°C) at Screening or check-in * Has a history or presence of drug or alcohol abuse within 24 months of Check-in * Pregnant or lactating females * Has used any prescription smoking cessation treatments within 3 months prior to Check-in * Is planning to quit smoking during the study or within the next 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Cmax | 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 | Maximum measured plasma nicotine concentration, baseline-adjusted |
| Nicotine AUCt | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urge to Smoke Pre-Use | 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'. |
| Urge to Smoke Post-Use | At 240 min following the start of study product use | 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'. |
| Smoking Urges Emax | 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. |
Countries
United Kingdom
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: 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) | 6 |
| 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) | 6 |
| 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) | 6 |
| 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) | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Product Sequence ABCD | Product Sequence BDAC | Product Sequence CADB | Product Sequence DCBA | Total |
|---|---|---|---|---|---|
| Age, Continuous | 40.7 years STANDARD_DEVIATION 12.75 | 31.8 years STANDARD_DEVIATION 8.11 | 49.2 years STANDARD_DEVIATION 7.14 | 42.2 years STANDARD_DEVIATION 12.5 | 41.0 years STANDARD_DEVIATION 11.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 4 Participants | 4 Participants | 14 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 / 24 | 0 / 24 | 0 / 24 | 0 / 23 |
| other Total, other adverse events | 2 / 24 | 3 / 24 | 1 / 24 | 0 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 23 |
Outcome results
Primary
Nicotine AUCt
The area under the concentration time curve for nicotine, from time 0 to the last observed non-zero concentration, baseline-adjusted
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Nicotine AUCt | 746.00 ng*min/mL | Standard Deviation 271.24 |
| Product B | Nicotine AUCt | 586.50 ng*min/mL | Standard Deviation 192.03 |
| Product C | Nicotine AUCt | 585.00 ng*min/mL | Standard Deviation 191.16 |
| Product D | Nicotine AUCt | 1514.00 ng*min/mL | Standard Deviation 368.91 |
Primary
Nicotine Cmax
Maximum measured plasma nicotine concentration, baseline-adjusted
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Nicotine Cmax | 10.500 ng/mL | Standard Deviation 8.284 |
| Product B | Nicotine Cmax | 7.539 ng/mL | Standard Deviation 4.653 |
| Product C | Nicotine Cmax | 8.191 ng/mL | Standard Deviation 4.447 |
| Product D | Nicotine Cmax | 21.680 ng/mL | Standard Deviation 10.81 |
Secondary
Smoking Urges Emax
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.
Time frame: 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
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 | Smoking Urges Emax | 40.30 units on a scale | Standard Deviation 25.75 |
| Product B | Smoking Urges Emax | 32.90 units on a scale | Standard Deviation 27.13 |
| Product C | Smoking Urges Emax | 39.70 units on a scale | Standard Deviation 29.72 |
| Product D | Smoking Urges Emax | 49.80 units on a scale | Standard Deviation 30.1 |
Secondary
Urge to Smoke Post-Use
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'.
Time frame: At 240 min following the start of study product use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Urge to Smoke Post-Use | 61.4 units on a scale | Standard Deviation 28.4 |
| Product B | Urge to Smoke Post-Use | 67.5 units on a scale | Standard Deviation 26.3 |
| Product C | Urge to Smoke Post-Use | 71.3 units on a scale | Standard Deviation 21.7 |
| Product D | Urge to Smoke Post-Use | 67.5 units on a scale | Standard Deviation 24.8 |
Secondary
Urge to Smoke Pre-Use
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'.
Time frame: 10 minutes prior to the start of the product use session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Urge to Smoke Pre-Use | 63.8 Units on a scale | Standard Deviation 27.4 |
| Product B | Urge to Smoke Pre-Use | 57.8 Units on a scale | Standard Deviation 30.9 |
| Product C | Urge to Smoke Pre-Use | 64.2 Units on a scale | Standard Deviation 29.6 |
| Product D | Urge to Smoke Pre-Use | 62.8 Units on a scale | Standard Deviation 30.1 |