Nicotine uptake Not Applicable
Conditions
Interventions
Subjects will be randomised to one of ten randomisation sequences according to a balanced Latin square (Williams) design and use each of the following five investigational products once in accordance
Sponsors
JT International SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to give written informed consent for participation in the study 2. Healthy male or female subject aged 19-64 years inclusive 3. Body Mass Index (BMI) =18.5 and =30.0 kg/m² at Screening 4. Subject who currently smokes factory-made combustible cigarettes (the ISO tar yield =6 mg), who typically smokes at least 10 and a maximum of 30 cigarettes per day, who daily smokes the cigarettes (more than 5 days per week), and who has been smoking cigarettes for at least 1 year prior to the Screening 5. Positive urine cotinine test (>200 ng/ml) at Screening 6. Clinically normal medical history, physical findings, vital signs, ECG, low dose of computed tomography of lungs and laboratory values at the time of Screening, as judged by the Investigator 7. Subjects who are healthy, as judged by the Investigator, based on all available assessments at Screening and PK assessment days (safety laboratory testing, spirometry [forced expiratory volume in 1 second {FEV1} s/forced vital capacity {FVC} >0.7 at post-bronchodilator spirometry, post-bronchodilator FEV1 >80% predicted value, and post-bronchodilator FVC >0.8], vital signs, physical examination, 12-lead ECG, and medical history) 8. Subjects who are able to place a pouch of Nordic Spirit 9 mg between gum and lip, in a 30-minute period without discomfort (the subjects will be asked to try a pouch of Nordic Spirit 9 mg during Screening) 9. Women of childbearing potential (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 [oestrogen 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], IUD or IUS. Sexual abstinence is allowed when this is the preferred and usual lifestyle of the subject 10. Negative to the coronavirus infection (PCR test on Screening, and antigen test on the day of check-in to the study site)
Exclusion criteria
Exclusion criteria: 1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject’s ability to participate in the study 2. Any clinically significant illness, a medical/surgical procedure or trauma within 2 weeks prior to the first day of PK assessment 3. Malignancy within the past 5 years except for in situ removal of basal cell carcinoma 4. Any surgery within 6 months of the Screening visit that could negatively impact the subject's participation, as judged by the Investigator 5. Any planned major surgery within the duration of the study 6. Medical history of seizures (single occasions of febrile seizure in childhood excluded) 7. Clinically significant liver disease (including total bilirubin, alkaline phosphatase, LDH, AST or ALT) as judged by the Investigator Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C virus antibodies and HIV 8. Positive screen for drugs of abuse or alcohol at Screening or on admission to the Site prior to any use of the investigational product 9. Systolic blood pressure of >140 mmHg or diastolic blood pressure of >90 mmHg, at least 5 minutes in the seated position 10. Poor peripheral venous access, as judged by the Investigator 11. Female subjects who are pregnant or who are currently breastfeeding 12. History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator 13. Presence or history of drug abuse and/or anabolic steroids, as judged by the Investigator 14. Subjects who have used any tobacco/nicotine-containing products (including electronic cigarettes and heat-not-burn tobacco products) or NRT medications, other than factory-made combustible cigarettes within 14 days of Screening 15. Subjects who, prior to enrolment, are planning to quit tobacco use during the study period or are postponing a quit attempt to participate in the study. All subjects will be informed that they are free to quit tobacco use and withdraw from the study at any time 16. Any use of prescription or over-the-counter bronchodilator medication (e.g., inhaled or oral ß-adrenergic agonists, cholinolytics or theophylline) to treat a chronic condition within the 12 months prior to the first day of PK assessment 17. Any medication (prescription or over-the-counter [OTC]) within 14 days or within five half-lives of the drug (whichever was longer) prior to the first day of PK assessment, which has an impact on CYP2A6 activity 18. Plasma donation within one month of Screening or blood donation (or corresponding blood loss – 450 ml) during the 3 months prior to Screening 19. Planned treatment or treatment with another investigational product within 3 months prior to the first day of PK assessment. Subjects consented and screened but not dosed in previous phase I studies are not excluded 20. Subjects who are employed by the tobacco industry, the clinical site, or handle unprocessed tobacco as part of their job 21. Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma nicotine levels analyzed using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method for pharmacokinetic parameters using blood samples collected at pre-use (within 15 minutes before the start of investigational product use), 2 (only for combustible cigarettes), 5, 8, 10, 15, 20, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 6 and 8 hours relative to the start of investigational product use | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Vital signs (blood pressure and pulse rate) measured using a sphygmomanometer and a pulse oximeter at baseline, 5, 30 and 60 minutes after the start of investigational product use 2. Subjective effects measured using a modified version of the Product Evaluation Scale following a single use of the investigational product 3. Intent to use the product again measured using the Intent to Use the Product Again Questionnaire (visual analogue scale) following a single use of investigational products 4. Amount of nicotine released from Nordic Spirit products 6 mg, 9 mg and 12 mg measured using a validated ultra performance liquid chromatography (UPLC)-UV method following a single use of investigational products. The difference between the nicotine content of the unused/reference pouch and the pouch used in the study will be used to calculate the released amount of nicotine | — |
Countries
Poland
Contacts
Public ContactMarta Zakrzewska
Outcome results
None listed