A study to assess nicotine uptake into the blood from and liking of two tobacco heating products compared to cigarettes and a nicotine replacement therapy

Not Applicable

Completed

• Conditions: Cigarette smoking; Not Applicable; Tobacco smoking

• Registration Number: ISRCTN13439529
• Lead Sponsor: British American Tobacco (Investments) Ltd

Brief Summary

2022 Results article in https://pubmed.ncbi.nlm.nih.gov/36038580/ (added 01/09/2022)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-08-07
• Study Completion: 2018-09-30
• Last Update Posted: 12 September 2022

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

1. Signed informed consent form (ICF)
2. Aged 19-60 years old
3. Body mass index (BMI) of 18.5 to 30.0 kg/m², inclusive, and a body weight of at least 52 kg for males and 45 kg for females
4. Current smokers:
4.1. At least 10 cigarettes per day
4.2. Smoke conventional factory-made cigarettes
4.3. eCO = 10 ppm
4.4. Urinary cotinine = 200 ng/ml at screening
5. Current smokers of non-menthol cigarettes
6. Smoked their chosen brand for a minimum of 6 months and must have smoked for at least one year prior to screening
7. Normal (or abnormal and not clinically significant) laboratory values (biochemistry, haematology, urinalysis) at screening
8. Normal (or abnormal and not clinically significant) 12-lead ECG at screening
9. Normal (or abnormal and not clinically significant) findings at the screening physical examination
10. Willing to refrain from performing vigorous exercise for 2 days outside of their normal routine before screening and for the total study duration
11. Willing to abstain from alcohol for 24 hours before screening and the in-clinic evaluation;
12. Willing to avoid eating foods containing poppy seeds for 72 hours prior to screening and the in-clinic evaluation;
13. No childbearing potential at the time of the study for female participants (female participants of childbearing potential (i.e. not in menopausal status from at least one year or permanently sterilised) must have a negative serum pregnancy test at screening (to be confirmed by urine pregnancy test at each of the four study visits))
14. Ability to understand the requirements of the investigation
15. Willing to comply with all investigation procedures.

Exclusion Criteria

1. Acute illness (e.g. upper respiratory tract infection, viral infection, etc) requiring treatment within 4 weeks prior to screening
2. Used any nicotine or tobacco product other than commercially-manufactured cigarettes within 14 days prior to screening
3. Self-reported non-inhalers (smokers who draw smoke from the cigarette into the mouth and throat but who do not inhale)
4. Medical history of asthma or chronic obstructive pulmonary disease (COPD)
5. Used prescription or over-the-counter (OTC) bronchodilator medication (e.g. inhaled or oral ß-adrenergic agonists or anticholinergic agents) to treat a chronic condition within the 12 months prior to screening
6. Received any medications or substances which are known to be strong inducers or inhibitors of cytochrome P450 (CYP) enzymes within 14 days or 5 half-lives of the drug (whichever is longer) prior to screening
7. Donated any of the following:
7.1. = 450 ml of blood within 90 days prior to screening
7.2. Plasma in the 7 days prior to screening
7.3. Platelets in the 6 weeks prior to screening
8. Perform strenuous physical activity (exceeding the subject’s normal activity levels) within 2 days prior to screening and the in-clinic evaluation
9. Medical history of any surgical or medical condition which, in the opinion of the investigator may interfere with participation in the investigation, or may jeopardize the safety of the subject or their compliance with the protocol, or may otherwise affect the outcome of the investigation
10. Any relevant surgical treatment during the previous 3 months or planned during the investigation
11. Medical history of serious psychiatric disorders
12. Serum hepatitis, carriers of the hepatitis B surface antigen (HBsAg), carriers of the hepatitis C antibody or a positive result for the test for human immunodeficiency virus (HIV) antibodies
13. Pulmonary function tests showing a forced expiratory volume after 1 second [FEV1]/forced vital capacity [FVC] < 0.7, FEV1 < 80% predicted value, and FVC < 80% predicted value
14. Abnormal QTcB interval value in the 12-lead ECG at screening (i.e. > 470 msec in both males or females)
15. Intake of illicit drugs within 6 months prior to screening, as determined by the investigator, or positive urine drug screen at screening
16. History of alcohol abuse within 6 months prior to screening, as determined by the investigator, or positive alcohol screen at screening (alcohol screen may be performed via a breath test)
17. Pregnant or lactating women at screening
18. Women physiologically capable of becoming pregnant during the overall investigation duration, unless willing to use a highly effective method of contraception. Highly effective birth control methods include:
18.1. Combined hormonal contraception (containing oestrogen and progestogen) associated with the inhibition of ovulation (oral, intravaginal, transdermal)
18.2. Progestogen-only hormonal contraception associated with the inhibition of ovulation (oral, injectable, implantable)
18.3. Intrauterine device (IUD)
18.4. Intrauterine hormone-releasing system (IUS)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. Plasma nicotine pharmacokinetic parameters, assessed 240 minutes after the first puff:<br> 1.1. Cmax<br> 1.2. Tmax<br> 1.3. AUC0<br> 2. Product liking assessment, assessed using the Product Liking Questionnaire (PLQ), at 5 minutes prior to and at 3, 5, 9, 30, 60, 120 and 240 minutes after first puff during the PK session<br> 3. Intent to use product again, assessed using the Overall Intent to Use Again (OIUA) questionnaire at 240 minutes after first puff during the PK session<br> 4. Urge to smoke a cigarette, as measured using the Urge To Smoke (UTS) questionnaire at 5 minutes prior to and at 3, 5, 9, 15, 30, 45, 60, 90, 180 and 240 minutes after first puff during the PK session<br> 5. Urge to use the investigational product assessed using the Urge For Product (UFP) questionnaire at 5 minutes prior to and at 15 and 120 minutes after first puff during the PK session<br>

Secondary Outcome Measures

Name	Time	Method
<br> 1. Puff count during 5 minute investigational product use session<br> 2. Product evaluation using the Product Evaluation Scale (PES) at 5 minutes prior to and at 15 and 240 minutes after first puff during the PK session<br>