A Randomised, Cross-over, Relative Bioavailability Study of Nicotine Delivery and Nicotine Extraction From Oral Products

A Randomised, Cross-over, Relative Bioavailability Study of Nicotine Delivery and Nicotine Extraction From Oral Products (Traditional Snus, Conventional Cigarette and Three Oral Tobacco-free Nicotine Delivery Products)

This study is a randomised cross-over, open-label, confinement study conducted in 24 male or female snus and cigarette consumers. The study investigates 5 different nicotine containing products in a cross-over fashion. The study incorporates pharmacokinetics evaluation, nicotine extraction evaluation, subjective questionnaire assessments as well as safety evaluation.

During the study participation, subjects come for two visits to the clinic, including a 5-day confinement period.

Study Overview

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

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

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden, SE-752 37
    • CTC Clinical Trial Consultants AB (CTC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body Mass Index (BMI) ≥ 18.0 and ≤ 30.0 kg/m
• Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator
• Dual user of snus and conventional cigarettes for ≥1 year, with a minimum weekly consumption of two or more snus cans and >5 cigarettes, and who is willing and able to use brands with nicotine content ≥1%

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
• Positive for HIV, hepatitis B or C

• After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges:

  • Systolic blood pressure <90 or >140 mmHg, or
  • Diastolic blood pressure <50 or >90 mmHg, or
  • Pulse <40 or >90 bpm
• Alcohol or drug abuse
• Use, or history of use of anabolic steroids
• Allergy/hypersensitivity to drugs with a similar chemical structure or class to nicotine
• Excessive caffeine consumption (daily intake of >5 cups)
• Female subjects who are pregnant or breastfeeding

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
Other: ABCDE; Subjects use product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes on Day 1, then switch to use product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 min on Day 2, then product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 min on Day 3, then D (nicotine pouch, 10.6 mg/pouch) on Day 4 and finally E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette), smoked in approximately 5 minutes with puffs taken at regular intervals approximately 30 seconds apart, on Day 5. Subjects can use their assigned product ad libitum on each study day, after all study assessments are performed, until 10pm. A washout period of product abstinence is observed between products, overnight.	Other: A; Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes; Other Names: Product A; Other: B; Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes; Other Names: Product B; Other: C; Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes; Other Names: Product C; Other: D; Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes; Other Names: Product D; Other: E; Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes; Other Names: Product E
Other: BCDEA; Same as previous arm but in a different randomization order.	Other: A; Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes; Other Names: Product A; Other: B; Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes; Other Names: Product B; Other: C; Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes; Other Names: Product C; Other: D; Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes; Other Names: Product D; Other: E; Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes; Other Names: Product E
Other: CDEAB; Same as previous arm but in a different randomization order.	Other: A; Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes; Other Names: Product A; Other: B; Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes; Other Names: Product B; Other: C; Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes; Other Names: Product C; Other: D; Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes; Other Names: Product D; Other: E; Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes; Other Names: Product E
Other: DEABC; Same as previous arm but in a different randomization order.	Other: A; Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes; Other Names: Product A; Other: B; Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes; Other Names: Product B; Other: C; Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes; Other Names: Product C; Other: D; Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes; Other Names: Product D; Other: E; Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes; Other Names: Product E
Other: EABCD; Same as previous arm but in a different randomization order.	Other: A; Use of product A (ZoneX #2, white tobacco-free nicotine pouch, 5.8 mg nicotine/pouch) for 20 minutes; Other Names: Product A; Other: B; Use of product B (ZoneX #3, white tobacco-free nicotine pouch, 10.1 mg nicotine/pouch) for 20 minutes; Other Names: Product B; Other: C; Use of product C (Skruf snus fresh slim white, 10.9 mg nicotine/pouch) for 20 minutes; Other Names: Product C; Other: D; Use of product D (Nicotine pouch, 10.6 mg/pouch) for 20 minutes; Other Names: Product D; Other: E; Use of product E (Marlboro Gold, conventional cigarette, 0.8 mg nicotine/cigarette) for approximately 5 minutes; Other Names: Product E

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine Cmax	Maximum plasma concentration of nicotine (Cmax)	Pre-use and at 2, 5, 7, 15, 20, 30, 45, 60, 90 minutes, and 2, 4, 6 and 8 hours post use start
Nicotine AUCt	Area under the plasma nicotine concentration-time curve at the last timepoint measured (AUCt)	Pre-use and at 2, 5, 7, 15, 20, 30, 45, 60, 90 minutes, and 2, 4, 6 and 8 hours post use start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine Extraction	Extraction fraction (%) of nicotine in used product pouches after 20 minutes of use.	20 minutes

Collaborators and Investigators

• Sponsor: Imperial Brands PLC

Publications and helpful links

General Publications

• Chapman F, McDermott S, Rudd K, Taverner V, Stevenson M, Chaudhary N, Reichmann K, Thompson J, Nahde T, O'Connell G. A randomised, open-label, cross-over clinical study to evaluate the pharmacokinetic, pharmacodynamic and safety and tolerability profiles of tobacco-free oral nicotine pouches relative to cigarettes. Psychopharmacology (Berl). 2022 Sep;239(9):2931-2943. doi: 10.1007/s00213-022-06178-6. Epub 2022 Jun 23.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): January 20, 2021
• Study Completion (Actual): January 20, 2021

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: IB-OND-PKZX-01

Drug and device information, study documents

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