A study to investigate the delivery of nicotine in the bloodstream from seven variants of tobacco-free oral nicotine pouches (Modern oral products), for comparison to a commercial snus product
| ISRCTN | ISRCTN18038559 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18038559 |
| Secondary identifying numbers | BAT2119018 |
- Submission date
- 10/12/2019
- Registration date
- 27/05/2020
- Last edited
- 08/06/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
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
Contact information
Public
Karolinska Trial Alliance
Karolinska Universitetssjukhuset Huddinge
Avdelning M62
Huddinge
14186
Sweden
| Phone | +46 (0)8-58585880 |
|---|---|
| forsokspersonkta.karolinska@sll.se |
Scientific
British American Tobacco
R&D Centre
Regents Park Road
Southampton
SO15 8TL
United Kingdom
| Phone | +44 (0)2380 588802 |
|---|---|
| David_azzopardi@bat.com |
Study information
| Study design | Multi-centre randomised pharmacokinetic cross-over study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A multi-centre, randomised, cross-over, pharmacokinetic study of 8 oral nicotine products |
| Study objectives | 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(s) | 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 |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 21/10/2019 |
| Completion date | 30/11/2020 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 36 |
| Total final enrolment | 36 |
| Key inclusion criteria | Healthy daily user of smokeless snus or modern oral nicotine products aged 19-55 years |
| Key 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 |
| Date of first enrolment | 15/01/2020 |
| Date of final enrolment | 06/03/2020 |
Locations
Countries of recruitment
- Sweden
Study participating centres
Huddinge
14186
Sweden
Lund
22185
Sweden
Sponsor information
Industry
Globe House
4 Temple Place
London
WC2R 2PG
United Kingdom
| Phone | +44 (0)2078451000 |
|---|---|
| david_azzopardi@bat.com | |
| Website | www.bat.com |
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/10/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | To publish data once CSR is finalised |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version V3.0 | 06/04/2020 | 08/06/2020 | No | No |
Additional files
- ISRCTN18038559_PROTOCOL_V3.0_06Apr20.pdf
- Uploaded 08/06/2020
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.
