A study to assess nicotine pharmacokinetics for heated tobacco products and cigarettes

Not Applicable

• Conditions: Alternative consumer products for primary users of factory-made combustible cigarettes +/- other non-medicinal nicotine delivery products; Not Applicable

• Registration Number: ISRCTN11517760
• Lead Sponsor: JT International SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-21
• Last Update Posted: 3 June 2024
• Study Completion: 2024-10-29

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Male or female participants aged from 19 to 65 years inclusive at Screening Visit.
2. Participant lives in the UK.
3. Participant can read, understand and sign a Participant Information Sheet (PIS) and Informed Consent Form (ICF) and complete questionnaires written in English.
4. Participants with a negative COVID-19 test on Day -1.
5. Participant must be an established user of combustible cigarettes and report an average consumption of at least 10 manufactured combustible cigarettes per day for at least 12 months before the screening visit. Participants may use e-cigarettes or heated tobacco products in addition to combustible cigarettes, provided that combustible cigarettes are the participant’s primary source of nicotine consumption.
6. Participant has positive urine cotinine tests (> 200 ng/mL) at Screening Visit and Check-in.
7. Participant is healthy, as judged by the Principal Investigator (PI), based on all available assessments at the Screening Visit and Check-in (e.g., safety laboratory measures, spirometry [forced expiratory volume in 1 second {FEV1} s/forced vital capacity {FVC} = 0.7 at pre-bronchodilator and post-bronchodilator basal spirometry, post-bronchodilator FEV1 = 80% predicted value, and post-bronchodilator FVC = 0.8], vital signs, physical examination, 12-lead ECG, and medical history).
8. Participant is willing to comply with all investigation procedures.
9. Female participant of childbearing potential who must be willing to use 2 effective forms of contraception from the time of signing the ICF until 1 month following the last product use session on Day 3 or be surgically sterile for at least 3 months before the Screening Visit.
10. Male participant (and partner of childbearing potential) willing to use an effective form of contraception, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the participant) from the time of signing the ICF until completion of the post-study follow up telephone call.
11. Female participant of menopausal status confirmed by demonstrating at Screening that the serum level of the follicle-stimulating hormone (FSH) falls within the respective pathology reference range. In the event, that a participant’s menopausal status has been clearly established (for example, the participant indicates she has been amenorrhoeic for 10 years, confirmed by medical history, etc), but serum FSH levels are not consistent with a postmenopausal status, determination of the participant’s eligibility to be included in the study will be at the Investigator’s discretion following consultation with the Sponsor.
12. Participant who, before enrolment, is not planning to quit/reduce their cigarette/nicotine usage in the next 8 weeks. All participants will be informed that they are free to quit nicotine use and withdraw from the study at any time.

Exclusion Criteria

1. As per the Principal Investigator judgment, the participant cannot participate in the study for any reason (e.g., medical, psychiatric, poor peripheral venous access, and/or social reasons).
2. Participant is legally incompetent, physically or mentally incapable of giving consent (e.g., emergency situation, under guardianship, prisoners or participant who is involuntarily incarcerated).
3. Participant has a medical condition that requires smoking cessation, or clinically relevant diseases (including but not limited to gastrointestinal, renal, hepatic, neurological, haematological, endocrine, oncological, urological, immunological, pulmonary, and cardiovascular disease, or any other medical condition [including but not limited to clinically relevant abnormal laboratory parameters]) in the judgment of the Principal Investigator.
4. As per the Principal Investigator judgment, the participant has medical conditions which require or in the course of the study would have required, a medical intervention (e.g., the start of treatment, surgery, hospitalisation) which could have interfered with the study participation and/or study results.
5. Participant has a body mass index (BMI) <18.5 kg/ m2 or BMI =32.0 kg/m2 at the Screening Visit.
6. Participant has an acute illness (e.g., upper respiratory tract infection, viral infection, etc) requiring treatment within 4 weeks before Screening or on admission.
7. Participant has received any treatment with smoking cessation medications (e.g., Bupropion, Chantix or any form of nicotine replacement therapy) within 4 weeks before Check-in.
8. Participant has received medication (prescription or over-the-counter [OTC]) within 14 days or within 5 half-lives of the drug before Check-in that induces or inhibits CYP2A6 activity.
9. Participant has a positive alcohol test and/or participant has a history of alcohol abuse that could interfere with participant’s participation in study.
10. Participant has a positive urine drug test.
11. Participant has used an e-cigarette in which the e-liquid contains cannabis within 3 months before Check-in.
12. Participant has a positive serology test for human immunodeficiency virus (HIV) 1/2, hepatitis B, or hepatitis C.
13. Donation of 450 mL or more blood within the 3 months before first product use.
14. Participant is a current or former employee of the tobacco or vaping industry or is a first-degree relative (parent, sibling, child).
15. Participation in a New Chemical Entity (NCE) clinical study within the previous 3 months or five half-lives, whichever is longer, or a marketed drug clinical study within 30 days or five half-lives, whichever is longer, before the first product use. (Washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study).
16. Participant has previously participated in the same study at a different time (i.e., each participant can be included in the study population only once).
17. Female participant of childbearing potential who is pregnant or breastfeeding.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoints for this study are pharmacokinetic parameters derived from the analysis of plasma samples for the concentration of nicotine.<br><br>The parameters to be calculated are as follows:<br>1. Maximum observed plasma nicotine concentration (Cmax) following a single use.<br>2. Area under the plasma nicotine concentration versus time curve from time zero to 240 min post-start of a single use (AUC0-240) and to last observed non-zero concentration (AUC0-t).<br>3. Time of maximum observed plasma concentration (tmax) following a single use.<br><br>Assessment Days 1, 2 & 3: Blood samples will be taken at the following timepoints: pre-dose (5 min before the start of single use), 2, 5, 7, 10, 15, 30, 60, 120 and 240 minutes relative to the start of single use of the assigned product on each day.