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

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

Contacts and Locations

• Study Contact: Name: Alvaro-Flavio Marinas Lacasta; Phone Number: +44 117 3322447; Email: alvaro-flavio.marinaslacasta@uk.imptob.com

Study Locations

• United Kingdom
  • Belfast, United Kingdom
    • Recruiting
    • Celerion
    • Contact: Devinda Weeraratne, Dr; Phone Number: +44 28 90 554040

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: Pulze device 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: Pulze device 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: Pulze device 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: Pulze device 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.; 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.
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: Pulze device 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: Pulze device 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: Pulze device 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: Pulze device 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.; 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.
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: Pulze device 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: Pulze device 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: Pulze device 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: Pulze device 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.; 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.
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: Pulze device 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: Pulze device 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: Pulze device 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: Pulze device 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.; 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.
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: Pulze device 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: Pulze device 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: Pulze device 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: Pulze device 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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine Cmax	Maximum measured plasma nicotine concentration, for 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, for 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
Smoking urges Emax	The maximum change from baseline Visual Analog Scale (VAS) score (VASpre-use - VASpost-use). Subjects answer the question "Right now, how much would you like to smoke a cigarette?" on a VAS: from Not at all on the left (0%) to A great deal on the right (100%), for the controlled product use session.	10 minutes prior to the start of the product use session, and at 4, 8, 15, 45, 60, 120 and 240 following the start of study product use minutes
Puff count	Number of puffs taken during 2 hours of the 4-hour ad-libitum product use session	2 hours

Collaborators and Investigators

• Sponsor: Imperial Brands PLC

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

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): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System 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