Nicotine use Other
Conditions
Interventions
Participants will report to the study site for a screening visit (Visit 1) followed by 11 treatment visits (Visits 2-12) on separate days. The screening will take place within 4 weeks before Visit 2.
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 oral tobacco/nicotine products for =1 year, with a minimum daily consumption of five or more pouches who are willing and able to use both tobacco-based moist snuff and NPs with high nicotine content 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. Successful completion of the product familiarization session for the comparator product use is required before the first IP administration. The subject should be able to follow the instructions, tolerate the product, and not experience any adverse effects different from what is expected during typical smokeless pouch use in the training session. 6. Female subjects of childbearing 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: 6.1. Combined (estrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) 6.2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 6.3. 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 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 administration. 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), 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 measured by baseline-adjusted area under the plasma concentration vs time curve from 0 to infinity (AUC0-inf) based on nicotine plasma concentrations. Blood samples will be collected at predefined timepoints: -10 min before IP administration, and at 5, 10, 15, 20, 30, 40, 60, 90, 120, 240, and 360 minutes post-IP administration. The goal is to demonstrate that the upper bound of the 90% confidence interval of the ratio for nicotine exposure of the new format unflavored NP 6 mg product and the comparator product is 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. Extraction from pouches: The difference in in vivo extracted amount (mg/unit) and extracted fraction (%) of nicotine between the unflavored NP 3 mg and 6 mg products and the comparator product, Longhorn Natural 18 mg. The IP pouches will be used for 30 minutes, 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 minutes of usage of the pouches from the mean of 10 unused pouches. 2. PK of nicotine in plasma: The difference between the unflavored NP 3 mg and 6 mg products and the comparator product, Longhorn Natural 18 mg, in the non-adjusted and baseline-adjusted PK parameters based on plasma concentrations of nicotine: 2.1. AUC0-inf 2.2. Maximum observed concentration (Cmax) 2.3. Time of occurrence of Cmax (Tmax) 2.4. AUC from 0 to 1.5 hours (AUC0-1.5h) 2.5. AUC from 0 to time of last measurable time point (AUC0-last) 2.6. Terminal elimination half-life (T1/2) 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. 3.1. PD (pulse rate): The difference between the unflavored NP 3 mg and 6 mg products and the comparator product, Longhorn Natural 18 mg, for the highest recorded increase (Emax) in pulse rate from baseline, measured using a pulse oximeter after IP administration. 3.2. PD parameters: The difference between the unflavored NP 3 mg and 6 mg products and the comparator product, Longhorn Natural 18 mg, for the highest recorded value (Emax) in the subjective parameters “craving” and “satisfaction”, measured using a 100 mm visual analogue scale (VAS) after IP administration. 3.3. PD (subjective outcome parameters): The difference between the unflavored NP 3 mg and 6 mg products and the comparator product, Longhorn Natural 18 mg, for the subjective p | — |
Countries
Sweden
Contacts
Public ContactCamilla Pramfalk
Outcome results
None listed