Condition category
Not Applicable
Date applied
10/12/2019
Date assigned
27/05/2020
Last edited
08/06/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Cigarette smoking is a leading cause of numerous human disorders including lung cancer, pulmonary disease and cardiovascular disease. Cigarette smoke is a complex and dynamic mixture of more than 6,500 identified chemical constituents, some of which have been identified as potential contributors to the disease-causing effects of cigarette smoke.
Recently, oral nicotine products containing little or no tobacco (henceforth referred to as ‘modern oral’) have emerged on the market as potential alternatives to existing oral tobacco products. One such product is “Lyft” (also known as “VELO” in certain markets), a smokeless, tobacco-free oral product which is white in colour and comes in pouches containing high-quality food-grade ingredients including naturally derived nicotine, water, cellulose, flavourings and sweeteners. Consumers place the pouch between their gum and upper lip, typically for up to 60 minutes. During use, nicotine and flavours are released and the nicotine is absorbed through the oral mucosa in the gum.
Research conducted by the sponsor suggests that Lyft modern oral products have a lower toxicant profile and reduced biological response compared to traditional tobacco-containing snus products. Therefore, understanding the rate of nicotine uptake is key information required to further characterise these products as potential alternatives to cigarette smoking and traditional snus use.
The aim of this study is to investigate the delivery and levels of nicotine in the bloodstream from seven variants of modern oral products and a snus product. From this, the researchers aim to obtain data to understand product efficacy at delivering nicotine, provide safety data, and to inform product design.

Who can participate?
Healthy adults aged 19-55 who are current daily users of snus or modern oral products

What does the study involve?
Participants will attend a screening visit to assess eligibility to participate in the study. Once deemed eligible, they will be admitted into the clinic (day -1) within 28 days of the screening visit, in which they will remain in the clinic for 8 days until discharge (day 8). During the participants stay at the clinic, they will be allowed to familiarise with the study products before their assessment. During the assessment period, they will use their assigned products for a maximum of 60 minutes. Before, during and up to 6 hours after product use, blood samples will be collected for nicotine analysis. A product satisfaction questionnaire and an overall intent to use again questionnaire will be completed at predefined intervals during this 6-hour period. The same procedure will be repeated on each study day until all the study products are used.

What are the possible benefits and risks of participating?
The possible benefit to participants taking part in this study is that the tests involved may help them learn about their general health or discover any unknown medical conditions. As participants already use tobacco products (snus or modern oral products), only the standard risks and side effects associated with nicotine and tobacco use apply. During study product use, it is not expected that subjects would be exposed to nicotine levels higher than those they are usually exposed to during their daily consumption of nicotine and tobacco products. The possible side effects of modern oral use include headache, dizziness, nausea, palpitations, mouth and throat irritation, skin irritation and gastrointestinal disturbances. Participants will be monitored for any of the listed symptoms.

Where is the study run from?
IRW Consulting (Sweden)

When is the study starting and how long is it expected to run for?
October 2019 to November 2020

Who is funding the study?
British American Tobacco (UK)

Who is the main contact?
David Azzopardi
david_azzopardi@bat.com

Trial website

Contact information

Type

Public

Primary contact

Dr Marika Kvarmstrom

ORCID ID

Contact details

Karolinska Trial Alliance
Karolinska Universitetssjukhuset Huddinge
Avdelning M62
Huddinge
14186
Sweden
+46 (0)8-58585880
forsokspersonkta.karolinska@sll.se

Type

Scientific

Additional contact

Dr David Azzopardi

ORCID ID

Contact details

British American Tobacco
R&D Centre
Regents Park Road
Southampton
SO15 8TL
United Kingdom
+44 (0)2380 588802
David_azzopardi@bat.com

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

BAT2119018

Study information

Scientific title

A multi-centre, randomised, cross-over, pharmacokinetic study of 8 oral nicotine products

Acronym

Study hypothesis

To determine the kinetics of nicotine absorption into the blood of subjects using different variants of smokeless nicotine products and to compare the nicotine PK parameters between smokeless nicotine products.

Ethics approval

Approved 05/03/2020, Central Swedish Ethics Committee (Etikprövningsmyndigheten, Box 2110, 750 02 Uppsala, Sweden; +46 (0)10 475 08 00; registrator@etikprovning.se), ref: 2019-06341

Study design

Multi-centre randomised pharmacokinetic cross-over study

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Nicotine uptake

Intervention

The following products will be administered in the study as 60-minute single product administrations:
1. Swedish Snus (pouch) – Granit Vit Stark with 13 mg/pouch nicotine
2. Lyft (commercial product), 4 mg/pouch
3. Lyft (commercial product), 10 mg/pouch
4. Lyft non-commercial (alginate removed), 10 mg/pouch
5. Lyft non-commercial (benzoic acid added), 4 mg/pouch
6. Lyft non-commercial (benzoic acid added), 10 mg/pouch
7. Lyft non-commercial (citric acid added), 10 mg/pouch
8. Lyft non-commercial (benzoic acid added, sweet base), 10 mg/pouch

Intervention type

Other

Phase

Drug names

Primary outcome measure

Plasma nicotine levels analysed for the following parameters using blood samples pre-dose (up to 5 minutes before the product use), and then at 5, 10, 20, 40, 60, 65, 75, 90, 120, 240 and 360 minutes following the start of administration:
1. Cmax
2. AUC0-6h

Secondary outcome measures

1. Product liking assessment, assessed using the Subjective Product Liking Questionnaire (PLQ) following product use
2. Intent to use product again, assessed using the Overall Intent to Use Again (OIUA) questionnaire following product use
3. Mouth Levels Exposure (MLE), assessed by measuring nicotine levels in pouches after use in PK session for comparison to unused products

Overall trial start date

21/10/2019

Overall trial end date

30/11/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Healthy daily user of smokeless snus or modern oral nicotine products aged 19-55 years

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

36

Total final enrolment

36

Participant exclusion criteria

1. Female who is lactating at screening
2. Female who is pregnant according to the pregnancy test at screening or prior to the first study product administration
3. Presence of braces, partials, dentures or any dental work that could, in the opinion of an investigator, affect the conduct of the study (including missing molars)
4. Presence or history of significant form of oral and/or pharyngeal inflammation, oral lesions and/or gum disease or temporomandibular joint dysfunction
5. History of significant hypersensitivity to any excipients of the formulations as well as severe hypersensitivity reactions (like angioedema) to any drugs
6. Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect nicotine bioavailability
7. History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
8. Presence of clinically significant ECG abnormalities at the screening visit, as defined by medical judgment
9. Maintenance therapy with any drug (with the exception of hormonal contraceptives or hormone replacement therapy) or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
10. Any clinically significant illness in the 28 days prior to the first study product administration
11. Use of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) in the 28 days prior to the first study product administration, that in the opinion of an investigator would put into question the status of the participant as healthy
12. Use of any medication or substance that aids in smoking cessation, including but not limited to any nicotine replacement therapy (e.g., nicotine gum, lozenge, patch), varenicline (Champix®), bupropion (Wellbutrin®, Zyban®), or Lobelia extract in the 28 days prior to the first study product administration
13. Any history of tuberculosis
14. Positive test result for alcohol and/or drugs of abuse at screening or prior to the first product administration
15. Positive screening results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or Hepatitis C Virus (HCV (C)) tests
16. Previous inclusion in this clinical study
17. Intake of an Investigational Product (IP) in any other clinical study in the 28 days prior to the first study product administration
18. Subjects who have donated:
18.1. ≥400 mL of blood within 90 days prior to admission
18.2. Plasma in the 7 days prior to admission
18.3. Platelets in the 6 weeks prior to administration
19. Postponement of a decision to quit using tobacco- or nicotine-containing products in order to participate in this study
20. Previously attempted to quit using tobacco- or nicotine-containing products in the 28 days prior to the first study product administration
21. Employees or immediate relatives of the tobacco industry or the clinical site

Recruitment start date

15/01/2020

Recruitment end date

06/03/2020

Locations

Countries of recruitment

Sweden

Trial participating centre

The Karolinska Trial Alliance (KTA) Phase I Unit
Karolinska Universitetssjukhuset Huddinge, Avdelning M62
Huddinge
14186
Sweden

Trial participating centre

The Skåne University Hospital, Clinical Studies Sweden – Forum South, Clinical Trial Unit
R&D Centre, Skane University Hospital, Skane
Lund
22185
Sweden

Sponsor information

Organisation

British American Tobacco (Investments)

Sponsor details

Globe House
4 Temple Place
London
WC2R 2PG
United Kingdom
+44 (0)2078451000
david_azzopardi@bat.com

Sponsor type

Industry

Website

www.bat.com

Funders

Funder type

Industry

Funder name

British American Tobacco

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

For-profit companies (industry)

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To publish data once CSR is finalised

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

31/10/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

08/06/2020: Uploaded protocol version 3.0, 6 April 2020 (not peer reviewed). 26/05/2020: Trial's existence confirmed by Central Swedish Ethics Committee.