A Relative Bioavailability Study of Nicotine Delivery From Selected Oral Nicotine Products

Imperial Brands PLC27 enrolled

Overview

This will be a randomised, cross-over, single-blind, confinement study conducted in 27 male or female snus or nicotine pouch users. The study will investigate 4 different nicotine containing products in a cross-over design, incorporating pharmacokinetic (PK) evaluation, nicotine extraction evaluation, subjective questionnaire assessments as well as safety and tolerability evaluation. During the study participation, subjects will come for 2 visits to the clinic, including a screening visit and a 4-day confinement period. A final follow up end-of-study telephone call will be performed within a week of last product use.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Healthy Volunteers

Interventions

Eligibility

Sex: ALLMin age: 19 YearsMax age: 99 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * BMI ≥ 18.0 and ≤ 30.0 kg/m2 * Clinically normal medical history * User of snus or nicotine pouches for ≥1 year, with a minimum weekly use of 2 or more snus or nicotine pouch cans and who is willing and considered able to use brands with nicotine content in the range of 14 to 20 mg nicotine/pouch Exclusion Criteria: * History of any clinically significant disease or disorder * Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first use of IP. * Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and HIV * Female subjects who are pregnant or breastfeeding * Presence or history of drug or alcohol abuse * Excessive caffeine consumption defined by a daily intake of \>5 cups of caffeine containing beverages * Intend to change nicotine-use habit or make a quit attempt within the next 3 months from the screening visit.

Outcomes

Primary Outcomes

Nicotine Cmax

Maximum observed plasma nicotine concentration

Time frame: 5 minutes prior to product use and 5, 10, 15, 20, 25, 30, 45, 60, 90 minutes, 2, 4, 6 and 8 hours post start of product use

Nicotine AUCt

The area under the concentration-time curve for nicotine, from time 0 to the time of the last sampling timepoint

Time frame: 5 minutes prior to product use and at 5, 10, 15, 20, 25, 30, 45, 60, 90 minutes, 2, 4, 6 and 8 hours post start of product use

Secondary Outcomes

Orally Extracted Amount of Nicotine

Orally extracted fraction of nicotine (%) in the pouch after the 20-minute use period.

Time frame: 20 minutes

Urge to Use Emax

The subjects will self-assess their urge to use a nicotine pouch, pre-use and after use, by answering the question: "How strong is your urge to use a nicotine pouch right now?" on a 100 mm visual analogue scale (VAS), with the anchor points 0 mm (= not at all/no urge) and 100 mm (= extremely/extreme urge). Emax is the maximum change from baseline VAS score (VASpre-use - VASpost-use).

Time frame: 5 minutes prior to product use and at 5, 10, 15, 20, 25, 30, 45 minutes, and 1, 1.5, 2, 4, 6 and 8 hours post start of product use