Healthy Volunteers
Conditions
Brief summary
This is a randomised, cross-over, open-label, confinement study conducted in 25 adult male or female smokers of combustible cigarettes (CCs). The study investigates combustible cigarettes, heated tobacco products (HTPs), and Heated Herbal Products (HHPs), with endpoints including pharmacokinetic evaluation, and subjective effects. Subjects will perform a Screening Visit and one Study Visit, including a 6-day confinement period.
Interventions
OTHERHeated tobacco product with heated tobacco sticks (Product A)
Product A, 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), followed by an ad-libitum, 4-hour product use session on the same day.
OTHERHeated tobacco product with heated tobacco sticks (Product B)
Product B, 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), followed by an ad-libitum, 4-hour product use session on the same day.
OTHERHeated herbal product with nicotine-infused heated herbal sticks (Product C)
Product C, 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), followed by an ad-libitum, 4-hour product use session on the same day.
OTHERHeated herbal product with nicotine-infused heated herbal sticks (Product D)
Product D, 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), followed by an ad-libitum, 4-hour product use session on the same day.
OTHERConventional Cigarette (Product E)
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), followed by an ad-libitum, 4-hour product use session on the same day.
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 * Female subjects of childbearing potential must use contraception * Male subjects 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 body mass index (BMI) \> 30.0 kg/m\^2 or \< 18.0 kg/m\^2 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, following the controlled product use session |
| 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, following the controlled product use session |
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: Right now, how much would you like to smoke a cigarette? on a Visual Analog Scale (VAS), with scores of 0 to 100, with 0 being 'not at all' and 100 being 'a great deal'. |
| Urge to Smoke Post-use | At 240 minutes following the start of study product use | The subjects self-assess their urge to smoke by answering the question: Right now, how much would you like to smoke a cigarette? on a Visual Analog Scale (VAS), with scores of 0 to 100, with 0 being 'not at all' and 100 being 'a great deal'. |
| Urge to Smoke Emax | 10 minutes prior to the start of the product use session and at 2, 4, 6, 8, 10, 15, 30, 45, 60, 120, 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: Right now, how much would you like to smoke a cigarette? on a Visual Analog Scale (VAS), with scores of 0 to 100, with 0 being 'not at all' and 100 being 'A great deal'. Emax is calculated as the maximum absolute value of change from baseline (pre-use) (i.e., the maximum response) in VAS scores. |
| Puff Count | Hours 2-4 of the 4-hour ad libitum product use session | Number of puffs taken during last 2 hours of the 4-hour ad-libitum product use session |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Product Use Sequence ABECD Subjects use Product A on Day 1, Product B on Day 2, Product E on Day 3 and Product C on Day 4 and Product D on Day 5. On each day, subjects completely use one single unit of the product (one stick, approximately 10 puffs, with 30-second interpuff intervals). | 5 |
| Product Use Sequence BCADE Subjects use Product B on Day 1, Product C on Day 2, Product A on Day 3 and Product D on Day 4 and Product E on Day 5. On each day, subjects completely use one single unit of the product (one stick, approximately 10 puffs, with 30-second interpuff intervals). | 5 |
| Product Use Sequence CDBEA Subjects use Product C on Day 1, Product D on Day 2, Product B on Day 3 and Product E on Day 4 and Product A on Day 5. On each day, subjects completely use one single unit of the product (one stick, approximately 10 puffs, with 30-second interpuff intervals). | 5 |
| Product Use Sequence DECAB Subjects use Product D on Day 1, Product E on Day 2, Product C on Day 3 and Product A on Day 4 and Product B on Day 5. On each day, subjects completely use one single unit of the product (one stick, approximately 10 puffs, with 30-second interpuff intervals). | 5 |
| Product Use Sequence EADBC Subjects use Product E on Day 1, Product A on Day 2, Product D on Day 3 and Product B on Day 4 and Product C on Day 5. On each day, subjects completely use one single unit of the product (one stick, approximately 10 puffs, with 30-second interpuff intervals). | 5 |
| Total | 25 |
Baseline characteristics
| Characteristic | Product Use Sequence ABECD | Product Use Sequence BCADE | Product Use Sequence CDBEA | Product Use Sequence DECAB | Product Use Sequence EADBC | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 46.4 years STANDARD_DEVIATION 9.91 | 39.4 years STANDARD_DEVIATION 8.62 | 43.2 years STANDARD_DEVIATION 8.7 | 36.4 years STANDARD_DEVIATION 12.58 | 37.8 years STANDARD_DEVIATION 6.06 | 40.6 years STANDARD_DEVIATION 9.38 |
| Body Mass Index (BMI) | 25.46 kg/m^2 STANDARD_DEVIATION 3.11 | 25.43 kg/m^2 STANDARD_DEVIATION 1.57 | 25.63 kg/m^2 STANDARD_DEVIATION 3.85 | 22.80 kg/m^2 STANDARD_DEVIATION 2.72 | 26.15 kg/m^2 STANDARD_DEVIATION 3.34 | 25.10 kg/m^2 STANDARD_DEVIATION 3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 25 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 15 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 / 25 | 0 / 25 | 0 / 25 | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 4 / 25 | 6 / 25 | 5 / 25 | 3 / 25 | 7 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 | 0 / 25 | 0 / 25 | 0 / 25 |
Outcome results
Primary
Nicotine AUCt
The area under the concentration time curve for nicotine, from time 0 to the last observed non-zero concentration, following the controlled product use session
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Nicotine AUCt | 716.3 ng*min/mL | Standard Deviation 329.6 |
| Product B | Nicotine AUCt | 777.0 ng*min/mL | Standard Deviation 289.4 |
| Product C | Nicotine AUCt | 363.9 ng*min/mL | Standard Deviation 123.8 |
| Product D | Nicotine AUCt | 382.5 ng*min/mL | Standard Deviation 145 |
| Product E | Nicotine AUCt | 1144.0 ng*min/mL | Standard Deviation 427.9 |
Primary
Nicotine Cmax
Maximum measured plasma nicotine concentration, following the controlled product use session
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Nicotine Cmax | 13.00 ng/mL | Standard Deviation 9.8 |
| Product B | Nicotine Cmax | 12.97 ng/mL | Standard Deviation 7.1 |
| Product C | Nicotine Cmax | 6.00 ng/mL | Standard Deviation 3.28 |
| Product D | Nicotine Cmax | 6.87 ng/mL | Standard Deviation 3.24 |
| Product E | Nicotine Cmax | 18.51 ng/mL | Standard Deviation 10.05 |
Secondary
Puff Count
Number of puffs taken during last 2 hours of the 4-hour ad-libitum product use session
Time frame: Hours 2-4 of the 4-hour ad libitum product use session
Population: Topography parameters were only available for subsets of subjects due to technical issues with the puff topography analyser during the data recording process, which resulted in incomplete data capture for some participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Puff Count | 30.3 number of puffs | Standard Deviation 18.7 |
| Product B | Puff Count | 22.4 number of puffs | Standard Deviation 14.3 |
| Product C | Puff Count | 32.4 number of puffs | Standard Deviation 20.8 |
| Product D | Puff Count | 31.9 number of puffs | Standard Deviation 13.7 |
| Product E | Puff Count | 20.2 number of puffs | Standard Deviation 10 |
Secondary
Urge to Smoke Emax
The subjects self-assess their urge to smoke at defined time points by answering the question: Right now, how much would you like to smoke a cigarette? on a Visual Analog Scale (VAS), with scores of 0 to 100, with 0 being 'not at all' and 100 being 'A great deal'. Emax is calculated as the maximum absolute value of change from baseline (pre-use) (i.e., the maximum response) in VAS scores.
Time frame: 10 minutes prior to the start of the product use session and at 2, 4, 6, 8, 10, 15, 30, 45, 60, 120, and 240 minutes following the start of study product use.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Urge to Smoke Emax | 56.0 units on a scale | Standard Deviation 29 |
| Product B | Urge to Smoke Emax | 64.4 units on a scale | Standard Deviation 29 |
| Product C | Urge to Smoke Emax | 43.0 units on a scale | Standard Deviation 31.7 |
| Product D | Urge to Smoke Emax | 44.3 units on a scale | Standard Deviation 28.9 |
| Product E | Urge to Smoke Emax | 69.2 units on a scale | Standard Deviation 28.4 |
Secondary
Urge to Smoke Post-use
The subjects self-assess their urge to smoke by answering the question: Right now, how much would you like to smoke a cigarette? on a Visual Analog Scale (VAS), with scores of 0 to 100, with 0 being 'not at all' and 100 being 'a great deal'.
Time frame: At 240 minutes following the start of study product use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Product A | Urge to Smoke Post-use | 91.4 units on a scale | Standard Deviation 13.3 |
| Product B | Urge to Smoke Post-use | 90.7 units on a scale | Standard Deviation 11.9 |
| Product C | Urge to Smoke Post-use | 88.7 units on a scale | Standard Deviation 15.5 |
| Product D | Urge to Smoke Post-use | 88.3 units on a scale | Standard Deviation 18.6 |
| Product E | Urge to Smoke Post-use | 87.6 units on a scale | Standard Deviation 18.2 |
Secondary
Urge to Smoke Pre-use
The subjects self-assess their urge to smoke by answering the question: Right now, how much would you like to smoke a cigarette? on a Visual Analog Scale (VAS), with scores of 0 to 100, with 0 being 'not at all' and 100 being 'a great deal'.
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 | 93.6 units on a scale | Standard Deviation 10.7 |
| Product B | Urge to Smoke Pre-use | 94.0 units on a scale | Standard Deviation 8.2 |
| Product C | Urge to Smoke Pre-use | 92.9 units on a scale | Standard Deviation 8.8 |
| Product D | Urge to Smoke Pre-use | 91.9 units on a scale | Standard Deviation 13 |
| Product E | Urge to Smoke Pre-use | 90.0 units on a scale | Standard Deviation 17.8 |