Nicotine use Other
Conditions
Interventions
Investigational Product (IP), dosage and mode of administration
1. ZYN ULTRA Wintergreen containing 9 mg nicotine per portion (1 pouch)
2. ZYN ULTRA Cool Mint containing 9 mg nicotine per portion (1
Sponsors
Swedish Match
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, preferably brands with nicotine content =1%, and is willing and able to use brands with nicotine content =1% 3. Healthy male or female subject aged =19 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. WOCBP 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 or presence of diagnosed hypertension or any cardiovascular disease. 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 investigational product 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 severe allergy/hypersensitivity or ongoing allergy/hypersensitivity to similar flavoring agents as those found in the IPs (e.g. spearmint in toothpaste) as judged by the investigator. Clinical Study Protocol SM20-02 Final v1.0; 07DEC2020 CONFIDENTIAL 28 (55) 6. Positive screen for drugs of abuse or alcohol at screening or on admission to the unit prior to first administration of the IP. Positive results that are expected given the subject’s medical history and prescribed medications can be disregarded as judged by the investigator. 7. Current or history of alcohol abuse and/or use of anabolic steroids or drugs of abuse, as judged by the investigator. 8. Plasma donation within one month of screening or blood donation (or corresponding blood loss) during the three months prior to screening. 9. Subjects who intend to change their nicotine consumption habit, including the intention to stop using nicotine products, within the next three months from the screening visit, as judged by the investigator. 10. The investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics of nicotine in plasma: the equivalence (90% confidence interval between 0.8 and 1.25) in AUCinf based on nicotine plasma concentrations from 0 to 6 h after the administration of single doses of ZYN ULTRA Smooth (unflavored) and ZYN ULTRA Wintergreen (flavored), calculated based on measurement of nicotine in blood samples with a liquid chromatography-mass spectrometry (LC-MS/MS) analytical method at the completion of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The difference in the highest recorded increase in pulse rate from baseline, measured using a pulse oximeter at pre-set time points up to 6 hours after IP administration (-10 min pre-dose, 5 min, 10 min, 15 min, 30 min, 45 min, 1 h, 1 h:15 min, 1 h:30 min, 2 h, 4 h, 6 h post-dose), between the unflavored ZYN ULTRA Smooth and the flavored ZYN ULTRA products 2. The difference in subjective parameters, measured using a 100 mm visual analogue scale (VAS) at pre-set time points up to 6 hours after IP administration (-10 min pre-dose, 5 min, 10 min, 15 min, 30 min, 45 min, 1 h, 1 h:15 min, 1 h:30 min, 2 h, 4 h, 6 h post-dose), between the unflavored ZYN ULTRA Smooth and the flavored ZYN ULTRA products 3. Pharmacokinetics of nicotine in plasma: the equivalence in Cmax and AUCinf based on nicotine plasma concentrations after the administration of single doses of ZYN ULTRA Smooth (unflavored) and the flavored ZYN ULTRA products, calculated based on measurement of nicotine in blood samples with a liquid chromatography-mass spectrometry (LC-MS/MS) analytical method at the completion of the study. Blood samples for analysis of PK parameters will be collected -10 min pre-dose, 5 min, 10 min, 15 min, 30 min, 45 min, 1 h, 1 h:15 min, 1 h:30 min, 2 h, 4 h, 6 h post-dose 4. Pharmacokinetics of nicotine in plasma: the calculated difference in Tmax, AUC0-1.5h, AUC0-t, and T1/2 between the unflavored ZYN ULTRA Smooth and the flavored ZYN ULTRA products based on nicotine plasma concentrations, measured using liquid chromatography-mass spectrometry (LC-MS/MS) analytical method at the completion of the study, from samples collected -10 min pre-dose, 5 min, 10 min, 15 min, 30 min, 45 min, 1 h, 1 h:15 min, 1 h:30 min, 2 h, 4 h, 6 h post-dose 5. The difference in in vivo extracted amount of nicotine (mg/unit) and extracted fraction (%) of nicotine between the unflavored ZYN ULTRA Smooth and the flavored ZYN ULTRA products analysed at t=60 min (removal of pouch) using GC-MS analysis and c | — |
Countries
Sweden
Outcome results
None listed