Nicotine Pharmacokinetic Study of Heated Tobacco and Heated Herbal Products

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Other: Conventional Cigarette (Product E); Other: Heated tobacco product with heated tobacco sticks (Product A); Other: Heated tobacco product with heated tobacco sticks (Product B); Other: Heated herbal product with nicotine-infused heated herbal sticks (Product C); Other: Heated herbal product with nicotine-infused heated herbal sticks (Product D)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom
    • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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
• 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

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: Conventional 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.; Other: Heated 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.; Other: Heated 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.; Other: Heated 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.; Other: Heated 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.
Experimental: 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.	Other: Conventional 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.; Other: Heated 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.; Other: Heated 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.; Other: Heated 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.; Other: Heated 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.
Experimental: 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.	Other: Conventional 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.; Other: Heated 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.; Other: Heated 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.; Other: Heated 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.; Other: Heated 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.
Experimental: 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.	Other: Conventional 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.; Other: Heated 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.; Other: Heated 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.; Other: Heated 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.; Other: Heated 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.
Experimental: 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.	Other: Conventional 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.; Other: Heated 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.; Other: Heated 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.; Other: Heated 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.; Other: Heated 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine Cmax	Maximum measured plasma nicotine concentration, following the controlled product use session	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, following the controlled product use session	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: "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'.	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: "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'.	At 240 minutes following the start of study product use
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.	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.
Puff Count	Number of puffs taken during last 2 hours of the 4-hour ad-libitum product use session	Hours 2-4 of the 4-hour ad libitum product use session

Collaborators and Investigators

• Sponsor: Imperial Brands PLC

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2023
• Primary Completion (Actual): November 3, 2023
• Study Completion (Actual): November 3, 2023

Study Registration Dates

• First Submitted: October 10, 2023
• First Submitted That Met QC Criteria: October 19, 2023
• First Posted (Actual): October 23, 2023

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: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: NER 01/005

Drug and device information, study documents

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