Nicotine use Other
Conditions
Interventions
Investigational products (IPs):
Nicotine pouch (NP) 1 - Dry, flavor A – 3 mg
NP 2 – Moist, flavor B – 3 mg
NP 3 – Moist, unflavored – 3 mg
T1 – Tobacco-based snus 1 – 4 mg
T2 – Tobacco-based sn
Sponsors
Swedish Match North Europe AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to give written informed consent for participation in the study. 2. Subjects who have used Swedish snus and/or NP products for =1 year, with a minimum daily consumption of five pouches, and who are willing and able to use both oral tobacco-based and NP products while abstaining from other tobacco/nicotine products during the study. 3. Healthy male or female subjects aged 21 to 60 years, inclusive. 4. Medically healthy subject without abnormal clinically significant medical history, physical findings, vital signs, ECG, and hepatitis B/C and human immunodeficiency virus (HIV) results at the time of the screening visit, as judged by the Investigator. 5. Female subjects of childbearing potential must either practice abstinence from heterosexual intercourse (if this is their consistent practice) or agree to use a highly effective method of contraception with a failure rate of <1% to prevent pregnancy for the duration of the study. The following are considered highly effective methods of contraception: 5.1. Combined (estrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) 5.2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 5.3. Intrauterine device or intrauterine hormone-releasing system
Exclusion criteria
Exclusion criteria: 1. A history of diagnosed hypertension or any cardiovascular disease, or ongoing manifestations of hypertension or any cardiovascular disease as judged by the Investigator. 2. Any surgical or medical condition, including abnormal salivation (also pharmaceutically induced), or history thereof, which, in the judgment of the Investigator, might interfere with the absorption, distribution, metabolism, or excretion of the IP or may either put the subject at risk because of participation in the study, influence the results, or the subject’s ability to participate in the study. 3. A history of diagnosed severe allergy/hypersensitivity or ongoing manifestations of severe allergy/hypersensitivity to aroma compounds (including fragrances and/or flavorings), as judged by the Investigator. 4. Subjects with poor venous access or being scared of needles. 5. Any planned major surgery within the duration of the study. 6. Subjects who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the study. 7. Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis B and C antibodies, and/or HIV. 8. Positive result for drugs of abuse or alcohol at the screening visit or on admission to the study site prior to IP use. Positive results that are expected given the subject’s medical history and prescribed medications can be disregarded as judged by the Investigator. 9. History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator. 10. Presence or history of drug abuse, as judged by the Investigator. 11. History of, or current use of anabolic steroids, as judged by the Investigator. 12. Current, ongoing use of beta-adrenergic blocking agents (beta blockers) or attention deficit hyperactivity disorder (ADHD) medications, including pro re nata (as needed) use. 13. Plasma donation within 1 month of screening or blood donation (or corresponding blood loss) during the last 3 months prior to screening. 14. Subjects who intend to change their nicotine consumption habit, including the intention to stop using nicotine products, within the next 3 months of the screening visit, as judged by the Investigator. 15. The Investigator considers the subject unlikely to comply with study procedures, restrictions, and requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Similarity in baseline-adjusted Cmax based on nicotine plasma concentrations after administering single doses of the three NP products and the two tobacco-based products. This is calculated based on the measurement of nicotine in plasma samples using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method at the end of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Equivalence (90% confidence interval for the ratio between 0.8 and 1.25) in baseline-adjusted Cmax and area under the curve (AUC) from 0 to infinity (AUC0-inf) based on nicotine plasma concentrations after administering single doses of the three NP products and the two tobacco-based products. This is calculated based on the measurement of nicotine in plasma samples using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method at the end of the study. 2. The difference in in vivo extracted amount (mg/unit) and extracted fraction (%) of nicotine between the three NP products and the two tobacco-based products. The IP pouches will be used for 30 minutes, collected, and frozen prior to analysis using GC-MS at the end of the study. The in vivo extraction of nicotine will be calculated by subtracting the residual amount of nicotine after 30 minutes of usage of the pouches from the mean of 10 unused pouches. 3. The difference between the three NP products and the two tobacco-based products in the non-adjusted and baseline-adjusted PK parameters: AUC0inf, Cmax, time of occurrence of Cmax (Tmax), AUC from 0 to 1.5 h (AUC0-1.5h), AUC from 0 to the last measurable time point (AUC0- last), and terminal elimination half-life (T½). This is calculated based on the measurement of nicotine in plasma samples using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method at the end of the study. 4. PD (pulse rate): The difference between the three NP products and the two tobacco-based products for the highest increase from baseline (Eimax), time to the first instance of Eimax (TEimax), the Emax from time 0 to 60 min (Emax0-60), and the time to reach Emax0-60 (TEmax0-60) in pulse rate, measured using a pulse oximeter after IP administration. 5. PD parameters: The difference between the three NP products and the two tobacco-based products for the largest decrease from baseline (Edmax) and time to the first instance of | — |
Countries
Sweden
Contacts
Public ContactCamilla Pramfalk
Outcome results
None listed