Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine and Nicotine Analogues

Обзор

Electronic cigarettes are battery-operated devices that can produce an aerosol by heating a liquid which commonly contains nicotine. In recent years, products containing synthetically produced nicotine and nicotine analogues have entered the market. However, it remains unclear whether these types of nicotine have the same effects as conventional nicotine derived from the tobacco plant. The aim of this study is to investigate the effects of these nicotine types and to gain a better understanding of their respective mechanisms of action.

Подробное описание

In the first part of the study, participants will use electronic cigarettes containing synthetic nicotine or nicotine analogs at three sessions in the hospital, following a specific schedule. In the second part, each product will be used for four days outside the hospital. The study is double-blind, meaning neither the participants nor the study team will know which product is being used.

The study comprises a total of seven appointments at the hospital. During these appointments, participants will be asked questions about their electronic cigarette and tobacco use, and samples of saliva, urine, and blood will be collected.

Вмешательства

• Другое Vaping of synthetic S-nicotine
  Vaping of e-liquids containing synthetic S-nicotine
• Другое Vaping of racemic nicotine (S-/R-nicotine)
  Vaping of e-liquids containing synthetic racemic nicotine (S-/R-nicotine)
• Другое Vaping of 6-methylnicotine
  Vaping of e-liquids containing the nicotine analogue 6-methylnicotine (6MN)

Первичные конечные точки

• Maximum total nicotine concentrations (Cmax) [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]

Вторичные конечные точки (12)

• Maximum concentration (Cmax) of 6-methylnicotine [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]
• Maximum concentration (Cmax) of 6-methylnicotine's metabolites [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]
• AUC (area under the concentration-time curve) nicotine enantiomers [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]
• AUC (area under the concentration-time curve) 6-methylnicotine [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]
• AUC (area under the concentration-time curve) 6-methylnicotine's metabolites [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]
• Tmax (time of Cmax) nicotine enantiomers [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]
• Tmax (time of Cmax) 6-methylnicotine [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]
• Tmax (time of Cmax) 6-methylnicotine's metabolites [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]
• T1/2 (elimination half-life) nicotine enantiomers [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]
• T1/2 (elimination half-life) 6-methylnicotine [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]
• T1/2 (elimination half-life) 6-methylnicotine's metabolites [Срок оценки: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff]
• Blood nicotine metabolite ratio (NMR) [Срок оценки: 15 minutes before vaping]

Критерии участия

Критерии включения

• Men or women, age 18 or older at screening who have used EC with nicotine during at least 10 of the past 30 days
• Saliva cotinine concentration of > 30 ng/mL at screening
• Ability to communicate well with the investigator and to understand and comply with the requirements of the study
• Women of child-bearing age engaging in sexual activities which can lead to pregnancy: willingness of using a reliable/hormonal contraception method during the study (hormonal, e.g. pill, intrauterine devices, or mechanical method, e.g. condom, diaphragm)
• Signed informed consent form

Критерии исключения

• Known hypersensitivity/allergy to a content of the e-liquids
• Smoking of more than 5 cigarettes per day in the past 30 days
• Pregnant or lactating women
• Intention to become pregnant during the course of the study
• BMI < 18 or > 30 kg/m2 at screening
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening
• Loss of ≥ 250 mL of blood within 3 months prior to screening, including blood donation
• Treatment with an investigational drug within 30 days prior to screening
• Treatment with prescribed or over-the-counter medications with known influence on CYP2A6 function within 1 week prior to screening (with the exception of contraception)
• History or clinical evidence of any disease (e.g. gastrointestinal tract-disease) and/or existence of any surgical or medical condition, which in the opinion of the investigator might interfere with the absorption, distribution, metabolism or excretion of the study drugs, or which might increase the risk of toxicity.
• Legal incapacity or limited legal capacity at screening
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Другое

Центры проведения

Швейцария · 1 центр

• Inselspital — Bern

Идентификаторы

NCT: NCT07348224 · BASEC-ID 2025-01893

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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