Nicotine use Other
Conditions
Interventions
Investigational product (IP) and dosage (oral smokeless nicotine pouch):
ZYN Dry Smooth, containing 6 mg nicotine per pouch (unflavored comparator product)
ZYN Dry Virginia Blend, containing 6 mg nico
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, and who are willing and able to use products with nicotine content =1 % 3. Healthy male or female subject aged =21 years 4. Clinically normal medical history, physical findings, vital signs, ECG, and laboratory values at the time of screening, as judged by the Investigator 5. Female subjects of child-bearing potential must be willing to use a sufficient contraceptive method for the duration of the study, this includes mechanical barrier (e.g., a male condom or a female diaphragm), combined [estrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal anticonception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device (IUD) or intrauterine system (IUS). Sexual abstinence is allowed when this is the preferred and usual lifestyle of the subject
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. Subjects who are pregnant, breastfeeding, or intend to become pregnant during the course of the study 4. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV) 5. 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 6. Positive screen for drugs of abuse or alcohol at screening or on admission to the unit prior to first IP administration. Positive results that are expected given the subject’s medical history and prescribed medications can be disregarded as judged by the Investigator 7. Current, ongoing use of beta-adrenergic blocking agents (beta-blockers), including pro re nata (as needed) use 8. Current or history of alcohol abuse and/or use of anabolic steroids or drugs of abuse, as judged by the Investigator 9. Plasma donation within 1 month of screening or blood donation (or corresponding blood loss) during the 3 months prior to screening 10. Subjects who intend to change their nicotine consumption habit, including the intention to stop using nicotine products, within the next 3 months from the screening visit, as judged by the Investigator 11. The Investigator considers the subject unlikely to comply with study procedures, restrictions, and requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The equivalence (90% confidence interval between 0.8 and 1.25) in AUCinf based on nicotine plasma concentrations from 0 to 6 hours after the administration of single doses of unflavored ZYN Dry Smooth and flavored ZYN Dry Virginia Blend, calculated based on measurement of nicotine in blood samples with 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 unflavored ZYN Dry Smooth and the flavored ZYN Dry products analyzed at t=60 min (removal of pouch). The in vivo extraction of nicotine is calculated by subtracting the residual amount after use from the mean of 10 unused pouches. Used pouches are frozen and analyzed using gas chromatography mass spectrometry (GC-MS) at the end of the study 2. Pharmacokinetics of nicotine in plasma: The equivalence between the unflavored and flavored ZYN Dry products in the non-adjusted and baseline-adjusted pharmacokinetic parameters Cmax and AUCinf based on plasma concentrations of nicotine after the administration of single doses, calculated based on measurement of nicotine in blood samples with a liquid chromatography-mass spectrometry (LC-MS/MS) analytical method at the end of the study. Blood samples for analysis of pharmacokinetic parameters are collected up to 6 hours after IP administration (-10 min pre-dose, and 5 min, 10 min, 15 min, 30 min, 45 min, 1h, 1 h:15 min, 1 h:30 min, 2 h, 4 h, 6 h post-dose) 3. Pharmacokinetics of nicotine in plasma: The difference between the unflavored and flavored ZYN Dry products in the non-adjusted and baseline-adjusted pharmacokinetic parameters Tmax, AUC0-1.5h, and AUC0-last, measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method at pre-defined timepoints: pre-administration (within 15 min prior to dose), and 5 min, 10 min, 15 min, 30 min, 45 min, 60 min, 1 h:15 min, 1 h:30 min, 2 h, 4 h, and 6 h post-administration. 4. The difference between the unflavored and flavored ZYN Dry products for the highest recorded increase in pulse rate from baseline, measured using a pulse oximeter at pre-defined time points up to 6 hours after IP administration (-10 min pre-dose, and 5 min, 10 min, 15 min, 30 min, 45 min, 1 h, 1 h:15 min, 1h:30 min, 2 h, 4 h, 6 h post-dose) 5. The difference between the unflavore | — |
Countries
Sweden
Outcome results
None listed