Оценка воздействия HPHC на курильщиков, переходящих на THS/TP18 с различными вариантами устройств
Рандомизированное, контролируемое, открытое исследование с 6 параллельными группами для оценки воздействия выбранных вредных и потенциально вредных компонентов (HPHC) сигаретного (CIG) дыма у взрослых курильщиков, переходящих на системы нагревания табака (THS/TP18) с различными вариантами устройств, по сравнению с продолжением курения сигарет
This is a randomized, controlled, open-label, 6 parallel arms study to assess reduced exposure of biomarkers of exposure (BoE) of selected HPHC in smokers switching to TP18 (a prototype heated tobacco device) or THS relative to smokers who continue smoking CIG after 5 days of confinement period, followed by 2 days of pharmacokinetic (PK) period of single use of THS/TP18 and CIG, and followed by an ambulatory period.
Обзор исследования
Статус
Статус
Условия
Условия
Вмешательство/лечение
Вмешательство/лечение
Подробное описание
This randomized, controlled, open-label study comprises six parallel arms and is designed to evaluate reductions in biomarkers of exposure (BoE) to selected HPHCs in adult smokers switching toTP18 (a prototype heated tobacco device with four variants: THS1, THS2, THS3, THS4) or THS5 relative to smokers who continue smoking CIG after 5 days of confinement period followed by 2 days of pharmacokinetic (PK) period of single use of THS/TP18 and CIG, and followed by an ambulatory period.
During the 5-day confinement period, participants will be randomized to use only their assigned product and will operate their assigned devices (THS1, THS2, THS3, THS4, or THS5) with their corresponding sticks or continue smoking CIG ad libitum (6 arms in total).
In the subsequent 2-day PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. Participants randomized to the CIG arm at Baseline will not participate in this period.
During the ambulatory period, participants randomized to one of the TP18 versions at Baseline will be free to choose and use any TP18 variant at any time, ad libitum. Participants randomized at Baseline to TP18 will continue using THS ad libitum. Participants randomized to the CIG arm will only be smoking cigarettes, ad libitum.
Тип исследования
Тип исследования
Регистрация (Действительный)
Регистрация
Фаза
Фаза
- Непригодный
Контакты и местонахождение
Места учебы
-
-
-
Belfast, Соединенное Королевство, BT9 6AD
- Celerion
-
-
Критерии участия
Критерии приемлемости
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria:
- Participant has signed the ICF and understands the information provided in it.
- Participant is male or female and between 21 and 65 years old (inclusive).
- Participant has been a smoker for at least 2 years prior to the screening visit and is willing to switch to THS and TP18.
- Participant has smoked on average ≥10 commercially available CIGs/day over the last 30 days. Smoking status will be verified based on a urinary cotinine test (cotinine ≥200 ng/mL).
- Participant does not plan to quit smoking within the next three months.
- Participant is available for the entire study period and willing to comply with the study procedures, including product use assignments and periods of abstinence from any nicotine/tobacco-containing products, and willing to adhere to a standardized diet (during confinement period and during overnight stays on Day 30 and Day 60).
Exclusion Criteria:
- As per the Investigator's judgment, the participant cannot participate in the study for any reason other than medical (e.g., psychological, social reason).
- Participant is legally incompetent, or physically or mentally incapable of giving consent (e.g., in emergency situations, under guardianship, prisoners).
- Participant has a health condition which requires medication or any other clinically relevant finding based on available assessments from the Screening period (e.g., safety panel, pulmonary function test, vital signs, physical examination, ECG, and medical history), as determined by the Principal Investigator or designee.
- Participant experienced within 30 days prior to screening/admission a body temperature >37.9°C or an acute illness (e.g., upper respiratory-tract infection, viral infection, etc.).
- According to the Investigator's judgment, the participant has medical conditions that require or will require medical intervention (e.g., initiation of treatment, surgery, hospitalization) during the study period, which may interfere with study participation and/or study results.
- Participant uses medication that aids in smoking cessation.
- Participant experiences difficulty with venipuncture and/or poor venous access.
- Participant has a hemoglobin level < 11.0 g/dL for females and < 12.0 g/dL for males at the Screening visit.
- Participant has a positive nitrite urinary test at screening or on admission day (Day -2)
- Participant has donated blood or received whole blood or blood products within the past 3 months.
- BMI < 18.5 kg/m2 or ≥ 32.0 kg/m2.
- Positive serology test for HIV 1/2, HBV, or HCVa.
- Participant has a positive alcohol breath test and/or has a history of alcohol disorder that could interfere with their participation in the study.
- The participant has a positive urine drug test.
- Participant or one of their family members is a current or former employee of the tobacco industry, manufacturing or distributing e-cigarettes or other nicotine/tobacco-containing products.
- A participant or a family member is an employee of the investigational site or of any other parties involved in the study.
- Participant has participated in another clinical study within 30 days or within a period equivalent to five half-lives of the investigational product from that study, whichever is longer. .
- Participant has been previously screened or enrolled in this study (unless they are alternate subjects).
- Female participant is pregnant (does not have negative pregnancy tests at screening and/or at admission) or is breastfeeding.
- For women of childbearing potential only and males: participant does not agree to use an acceptable method of effective contraception.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Фундаментальная наука
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Количество рук
Оружие и интервенции
Группа участников / АрмияГруппа участников / Армия |
Вмешательство/лечениеВмешательство/лечение |
|---|---|
|
Другой: THS1
During the confinement period, participants will use only their assigned product THS 1 (with the corresponding sticks) ad libitum. During the PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. During the ambulatory period, they may choose any variant (THS1, THS2, THS3, or THS4) at any time, ad libitum. |
TP18 prototype variant "1" (THS1) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants. |
|
Другой: THS2
During the confinement period, participants will use only their assigned product THS 2 (with the corresponding sticks) ad libitum. During the PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. During the ambulatory period, they may choose any variant (THS1, THS2, THS3, or THS4) at any time, ad libitum. |
TP18 prototype variant "2" (THS2) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants. |
|
Другой: THS3
During the confinement period, participants will use only their assigned product THS 3 (with the corresponding sticks) ad libitum. During the PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. During the ambulatory period, they may choose any variant (THS1, THS2, THS3, or THS4) at any time, ad libitum. |
TP18 prototype variant "3" (THS3) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants. |
|
Другой: THS4
During the confinement period, participants will use only their assigned product THS 4 (with the corresponding sticks) ad libitum. During the PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. During the ambulatory period, they may choose any variant (THS1, THS2, THS3, or THS4) at any time, ad libitum. |
TP18 prototype variant "4" (THS4) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants. |
|
Другой: THS5
During the confinement period, participants will use only their assigned product THS 5 (with the corresponding sticks) ad libitum. During the PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. During the ambulatory period, they will be continue to use THS5 ad libitum. |
THS 3.0 device (reference) and the corresponding tobacco sticks will be provided by the Sponsor. There are two variants of the sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants may choose either variant or both. |
|
Другой: CIG
During the confinement period, participants will use only their usual brand of commercially available CIG ad libitum. This arm will not participate in the PK period and will move directly to the ambulatory period. During the ambulatory period, participants will smoke only cigarettes, ad libitum. |
Current cigarette smokers will use their usual brand of commercially available CIG. |
Что измеряет исследование?
Первичные показатели результатов
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
3-hydroxypropyl mercapturic acid (3-HPMA) in Urine (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Concentrations of 3-HPMA measured in 24-hour urine and expressed as concentration adjusted for creatinine. |
Measured from Day -1 to Day 5.
|
|
2-cyanoethyl mercapturic acid N-acetyl-S-(2-cyanoethyl)-L-cysteine (2-CyEMA) in Urine (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Concentrations of 2-CyEMA measured in 24-hour urine and expressed as concentration adjusted for creatinine. |
Measured from Day -1 to Day 5.
|
|
Monohydroxybutenyl mercapturic acid (MHBMA) in Urine (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Concentrations of MHBMA measured in 24-hour urine and expressed as concentration adjusted for creatinine. |
Measured from Day -1 to Day 5.
|
|
Total N-nitrosonornicotine (total NNN) in Urine (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Concentrations of total NNN measured in 24-hour urine and expressed as concentration adjusted for creatinine. |
Measured from Day -1 to Day 5.
|
|
Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in Urine (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Concentrations of total NNAL measured in 24-hour urine and expressed as concentration adjusted for creatinine. |
Measured from Day -1 to Day 5.
|
|
Carboxyhemoglobin (COHb) in Blood (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Carboxyhemoglobin (COHb) is assayed from whole blood and expressed as percentage of the total hemoglobin saturated with carbon monoxide. |
Measured from Day -1 to Day 5.
|
Вторичные показатели результатов
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
S-phenylmercapturic acid (S-PMA) in Urine (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Concentrations of S-PMA measured in 24-hour urine and expressed as concentration adjusted for creatinine. |
Measured from Day -1 to Day 5.
|
|
2-hydroxyethylmercapturic acid (2-HEMA) in Urine (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Concentrations of 2-HEMA measured in 24-hour urine and expressed as concentration adjusted for creatinine. |
Measured from Day -1 to Day 5.
|
|
3-hydroxy-1-methylpropylmercapturic acid (3-HMPMA) in Urine (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Concentrations of 3-HMPMA measured in 24-hour urine and expressed as concentration adjusted for creatinine. |
Measured from Day -1 to Day 5.
|
|
Total 3-hydroxybenzo(a)pyrene (3-OH-B[a]P) in Urine (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Concentrations of 3-OH-B[a]P measured in 24-hour urine and expressed as concentration adjusted for creatinine. |
Measured from Day -1 to Day 5.
|
|
4-aminobiphenyl (4-ABP) in Urine (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Concentrations of 4-ABP measured in 24-hour urine and expressed as concentration adjusted for creatinine. |
Measured from Day -1 to Day 5.
|
|
2-aminonaphtalene (2-NA) in Urine (confinement period)
Временное ограничение: Measured from Day -1 to Day 5.
|
Concentrations of 2-NA measured in 24-hour urine and expressed as concentration adjusted for creatinine. |
Measured from Day -1 to Day 5.
|
Другие показатели результатов
Другие показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Plasma nicotine concentrations [C0h] to [C6h] (pharmacokinetic period)
Временное ограничение: Measured from Day 6 to Day 7.
|
To measure the background-corrected plasma nicotine concentrations (C0h) to (C12h) |
Measured from Day 6 to Day 7.
|
|
Maximum plasma nicotine concentration [Cmax] (pharmacokinetic period)
Временное ограничение: Measured from Day 6 to Day 7.
|
To measure the background-corrected maximum plasma nicotine concentration [Cmax] |
Measured from Day 6 to Day 7.
|
|
Area under the plasma nicotine concentration-time curve (pharmacokinetic period)
Временное ограничение: Measured from Day 6 to Day 7.
|
To measure the area under the background-corrected plasma nicotine concentration-time curve (AUC) from the start of product use (T0) to the timepoint of last quantifiable concentration [AUC0-last] and extrapolated to infinity [AUC0-infinity] |
Measured from Day 6 to Day 7.
|
|
Maximum concentration [Tmax] (pharmacokinetic period)
Временное ограничение: Measured from Day 6 to Day 7.
|
To measure the time to the background-corrected maximum concentration [Tmax] |
Measured from Day 6 to Day 7.
|
|
3-hydroxypropyl mercapturic acid (3-HPMA) in Urine (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Concentrations of 3-HPMA measured in spot urine and expressed as concentration adjusted for creatinine. |
Measured on Day 30 and Day 60.
|
|
2-cyanoethyl mercapturic acid N-acetyl-S-(2- cyanoethyl)-L-cysteine (2-CyEMA) in Urine (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Concentrations of 2-CyEMA measured in spot urine and expressed as concentration adjusted for creatinine. |
Measured on Day 30 and Day 60.
|
|
Monohydroxybutenyl mercapturic acid (MHBMA) in Urine (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Concentrations of MHBMA measured in spot urine and expressed as concentration adjusted for creatinine. |
Measured on Day 30 and Day 60.
|
|
Total N-nitrosonornicotine (total NNN) in Urine (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Concentrations of total NNN measured in spot urine and expressed as concentration adjusted for creatinine. |
Measured on Day 30 and Day 60.
|
|
Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Concentrations of total NNAL measured in spot urine and expressed as concentration adjusted for creatinine. |
Measured on Day 30 and Day 60.
|
|
Carboxyhemoglobin (COHb) in Blood (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Carboxyhemoglobin (COHb) is assayed from whole blood and expressed as percentage of the total hemoglobin saturated with carbon monoxide. |
Measured on Day 30 and Day 60.
|
|
S-phenylmercapturic acid (S-PMA) in Urine (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Concentrations of S-PMA measured in spot urine and expressed as concentration adjusted for creatinine. |
Measured on Day 30 and Day 60.
|
|
2-hydroxyethylmercapturic acid (2-HEMA) in Urine (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Concentrations of 2-HEMA measured in spot urine and expressed as concentration adjusted for creatinine. |
Measured on Day 30 and Day 60.
|
|
3-hydroxy-1-methylpropylmercapturic acid (3-HMPMA) in Urine (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Concentrations of 3-HMPMA measured in spot urine and expressed as concentration adjusted for creatinine. |
Measured on Day 30 and Day 60.
|
|
Total 3-hydroxybenzo(a)pyrene (3-OH-B[a]P) in Urine (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Concentrations of 3-OH-B[a]P measured in spot urine and expressed as concentration adjusted for creatinine. |
Measured on Day 30 and Day 60.
|
|
4-aminobiphenyl (4-ABP) in Urine (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Concentrations of 4-ABP measured in spot urine and expressed as concentration adjusted for creatinine. |
Measured on Day 30 and Day 60.
|
|
2-aminonaphtalene (2-NA) in Urine (ambulatory period)
Временное ограничение: Measured on Day 30 and Day 60.
|
Concentrations of 2-NA measured in spot urine and expressed as concentration adjusted for creatinine. |
Measured on Day 30 and Day 60.
|
Соавторы и исследователи
Спонсор
Спонсор
Следователи
Следователи
- Учебный стул: Christelle Haziza, PhD, Philip Morris Products S.A.
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Начало исследования
Первичное завершение (Действительный)
Первичное завершение
Завершение исследования (Оцененный)
Завершение исследования
Даты регистрации исследования
Первый отправленный
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Первый опубликованный
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее опубликованное обновление
Последнее отправленное обновление, отвечающее критериям контроля качества
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
Другие идентификационные номера исследования
- P1-REX_PK-22
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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