Nicotine use Other
Conditions
Interventions
The screening visit (Visit 1) will take place within 5 weeks prior to start of Part 2 (Visit 4) and will include an eligibility check, including evaluations of smoking and oral tobacco/nicotine use, c
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 products for =1 year, with a minimum daily consumption of 5 pouches/portions, who are willing and able to use both Swedish pouch snus and NPs with high nicotine content while abstaining from other tobacco/nicotine products during the study. (Dual use of Swedish snus and NPs before inclusion will be permitted, but subjects should exclusively use their usual brand of a Swedish snus product (including strength and flavor) ad libitum during Part 1). 3. Healthy male or female subject aged 19 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 child-bearing potential must practice abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the subject) or must 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 who are 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 screening 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 |
|---|---|
| Nicotine exposure, as measured by baseline-adjusted area under the plasma concentration vs time curve from 0 to infinity (AUC0-inf) based on nicotine plasma concentrations, compared between the moist NP 11 mg product and the comparator product, Swedish snus 18 mg. (The goal is to demonstrate that the upper bound of the 95 % confidence interval for the ratio for nicotine exposure between the moist NP 11 mg product and the comparator product is at or below 1.25). 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. The difference in in vivo extracted amount (mg/unit) and extracted fraction (%) of nicotine between the moist NP 6 mg, 11 mg, and 16.6 mg products and the comparator products, Swedish snus 18 mg and own brand snus product. The IP pouches will be used for 30 min, collected, and frozen prior to analysis using gas chromatography - mass spectrometry (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 min of usage of the pouches from the mean of 10 unused pouches. 2.1. The difference between the moist NP 6 mg, 11 mg, and 16.6 mg products and the comparator products, Swedish snus 18 mg and own brand snus product, in the non-adjusted and baseline-adjusted PK parameters based on plasma concentrations of nicotine: 2.1.1. AUC0-inf 2.1.2. Maximum observed plasma concentration (Cmax) 2.1.3. Time to Cmax (Tmax) 2.1.4. AUC from 0 to 1.5 hours (AUC0-1.5h) 2.1.5. AUC from 0 to time of last measurable time point (AUC0-last) 2.1.6. Terminal elimination half-life (T1/2) This is calculated based on the measurement of nicotine in plasma samples using a validated LC-MS/MS analytical method at the end of the study. 2.2. Nicotine exposure, as measured by non-adjusted and baseline-adjusted AUC0-inf, compared between the moist NP 6 mg and NP 16.6 mg products and the comparator products, Swedish snus 18 mg, and the own brand snus product. This comparison also includes the NP 11 mg product and the own brand snus product. (The goal is to demonstrate that the upper bound of the 95% confidence interval for the ratio for nicotine exposure between the moist NP products and the comparator products is at or below 1.25). This is calculated based on the measurement of nicotine in plasma samples using a validated LC-MS/MS analytical method at the end of the study. 3.1. The difference between the moist NP 6 mg, 11 mg, and 16.6 mg products and the comparator products, Swedish snus 18 mg and own brand snus prod | — |
Countries
Sweden
Contacts
Public ContactCamilla Pramfalk
Outcome results
None listed