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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Other: Product A; Other: Product B; Other: Product C; Other: Product D

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Nothern Ireland
    • Belfast, Nothern Ireland, United Kingdom, BT9 6AD
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Other: 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); Other: 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); Other: 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); Other: 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)
Experimental: 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	Other: 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); Other: 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); Other: 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); Other: 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)
Experimental: 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	Other: 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); Other: 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); Other: 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); Other: 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)
Experimental: 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	Other: 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); Other: 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); Other: 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); Other: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine Cmax	Maximum measured plasma nicotine concentration, baseline-adjusted	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
Nicotine AUCt	The area under the concentration time curve for nicotine, from time 0 to the last observed non-zero concentration, baseline-adjusted	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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'.	10 minutes prior to the start of the product use session
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'.	At 240 min following the start of study product use
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.	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

Collaborators and Investigators

• Sponsor: Imperial Brands PLC

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): November 30, 2021

Study Registration Dates

• First Submitted: July 6, 2022
• First Submitted That Met QC Criteria: July 12, 2022
• First Posted (Actual): July 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Dermatologic Agents; Antipruritics; Menthol
• Other Study ID Numbers: NER01/0004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No