A Single-center, Randomized, Controlled, Openlabel, Cross-over Study in Currently Smoking Adult Participants to Investigate the Nicotine Pharmacokinetics and Pharmacodynamics of Tobacco Heating System (THS) With LEVIA, a Tobacco-free Nicotine-containing Product Compared to THS With TEREA, a Heated Tobacco Product and to Cigarettes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Background-corrected plasma nicotine concentrations (cC0h) to (cC12h)
研究概览
简要总结
A single-center, randomized, controlled, open-label, crossover study in currently smoking adult participants to investigate the nicotine pharmacokinetics and pharmacodynamics of Tobacco Heating System (THS) with LEVIA, a tobacco-free nicotine-containing consumable, compared to THS with TEREA, a tobacco-containing consumable, and cigarettes.
The study will use a 2-period, 2-sequence design for the ad libitum use days, and a 3-period, 6-sequence Williams design for the single-use days. Across the ad libitum use and single-use period, this is a design with 5 periods and 12 sequences.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant has signed the Informed Consent Form (ICF) and is able to understand the information provided in the ICF.
- •Male or female current (past 30 days) daily users of heated tobacco products and concomitantly smoking cigarettes aged between 21 and 65 years inclusive.
- •Participant has used heated tobacco products (no brand restriction) for at least the last 6 months prior to the Screening visit.
- •Participant has smoked commercially available or roll-your own cigarettes (no brand restrictions) for at least the last 12 months prior to the Screening visit.
- •Participant has used at least 10 heated tobacco products and/or commercially available cigarettes without any brand restriction or roll-your own cigarettes per day in the past 30 days prior to Screening visit and Admission.
- •Participant has a urinary cotinine concentration of ≥ 200 ng/mL.
- •Participant has a BMI >18.5 and <30.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.
- •Participant is available for the entire study period and willing to comply with study procedures, including product use assignments and periods of abstinence from any nicotine/tobacco containing products and willing to adhere to a standardized diet.
排除标准
- •Participant has reasons other than medical (e.g., psychological, social reason) not to be part of the study, as determined by the Principal Investigator or designee.
- •Participant is legally incompetent, or physically or mentally incapable of giving consent (e.g., emergency situation, under guardianship, prisoner).
- •Participant has a health condition that requires medication or any other clinically relevant finding based on the assessment from the Screening visit (e.g., safety laboratory, pulmonary function test, vital signs, physical examination, ECG, and medical history) as determined by the Principal Investigator or designee.
- •Participant experiences difficulty with venipuncture and/or poor venous access.
- •Participant has medical conditions which require, or will require during the study, a medical intervention (e.g., start of treatment, surgery, hospitalization).
- •Presence of fever (body temperature >37.5°C), e.g., a fever associated with a symptomatic viral or bacterial infection.
- •Participant has a hemoglobin level < 11.0 g/dL for females and < 12.0 g/dL for males at the Screening visit.
- •Participant uses medication that aids in smoking cessation.
- •Participant previously attempted to quit using tobacco- or nicotine-containing products within 28 days prior to the first investigational product use.
- •Participant has donated plasma within seven days prior to the Screening visit or has donated or lost 450 mL or more of whole blood within 8 weeks prior to the Screening visit for males, and in the 12 weeks prior to the Screening visit for females.
- •Participant has a known sensitivity or allergy to LEVIA or TEREA investigational products.
- •Participant has a positive serology test for HIV 1/2, hepatitis B or C.
- •Participant has a medical history of alcohol abuse within one year prior to the Screening visit or regular use of alcohol within six months prior to the Screening visit that exceeds 10 units for women or 15 units for men of alcohol per week.
- •Participant has a positive urine drug screen test. The Principal Investigator will assess whether THC-positive participants are eligible for study participation.
- •Participant has a positive alcohol breath test.
- •Participant or one of their family members is a current or former employee of the tobacco industry.
- •Participant or one of their family members is an employee of the investigational site or of any other parties involved in the study.
- •Participant has participated in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to investigational product use, the administration of a biological product in the context of a clinical research study within 90 days prior to the Screening visit, or concomitant participation in an investigational study involving no drug or device administration.
- •Participant has been previously screened or enrolled in this study (except overenrolled participants).
- •For women only: participant with positive urine pregnancy tests at the Screening visit or at Admission, or is a lactating female.
- •For women of childbearing potential only: participant does not agree to use an acceptable method of effective contraception throughout study participation.
研究组 & 干预措施
Ad libitum product use (day 1; day 2)
Participants will be simultaneously randomized to product use sequences for ad libitum use.
The list of possible sequences are:
- THS with LEVIA; THS with TEREA
- THS with TEREA; THS with LEVIA
干预措施: THS with LEVIA (ad libitum) (Other)
Ad libitum product use (day 1; day 2)
Participants will be simultaneously randomized to product use sequences for ad libitum use.
The list of possible sequences are:
- THS with LEVIA; THS with TEREA
- THS with TEREA; THS with LEVIA
干预措施: THS with TEREA (ad libitum) (Other)
Single product use (day 3; day 4; day 5)
Participants will be simultaneously randomized to product use sequences for single product use.
The list of possible sequences are:
- Cigarette; THS with LEVIA; THS with TEREA
- Cigarette; THS with TEREA; THS with LEVIA
- THS with LEVIA; Cigarette; THS with TEREA
- THS with LEVIA; THS with TEREA; Cigarette
- THS with TEREA; Cigarette; THS with LEVIA
- THS with TEREA; THS with LEVIA; Cigarette
干预措施: THS with LEVIA (Other)
Single product use (day 3; day 4; day 5)
Participants will be simultaneously randomized to product use sequences for single product use.
The list of possible sequences are:
- Cigarette; THS with LEVIA; THS with TEREA
- Cigarette; THS with TEREA; THS with LEVIA
- THS with LEVIA; Cigarette; THS with TEREA
- THS with LEVIA; THS with TEREA; Cigarette
- THS with TEREA; Cigarette; THS with LEVIA
- THS with TEREA; THS with LEVIA; Cigarette
干预措施: THS with TEREA (Other)
Single product use (day 3; day 4; day 5)
Participants will be simultaneously randomized to product use sequences for single product use.
The list of possible sequences are:
- Cigarette; THS with LEVIA; THS with TEREA
- Cigarette; THS with TEREA; THS with LEVIA
- THS with LEVIA; Cigarette; THS with TEREA
- THS with LEVIA; THS with TEREA; Cigarette
- THS with TEREA; Cigarette; THS with LEVIA
- THS with TEREA; THS with LEVIA; Cigarette
干预措施: Cigarette (Other)
结局指标
主要结局
Background-corrected plasma nicotine concentrations (cC0h) to (cC12h)
时间窗: Measured from Day 3 to Day 5
To measure the background-corrected plasma nicotine concentrations (cC0h) to (cC12h)
Background-corrected maximum plasma nicotine concentration (Cmax)
时间窗: Measured from Day 3 to Day 5
To measure the background-corrected maximum plasma nicotine concentration \[Cmax\]
Area under the background-corrected plasma nicotine concentration-time curve (AUC) (AUC) from the start of product use (T0) to the timepoint of last quantifiable concentration (AUC0-last) and extrapolated to infinity (AUC0-infinity)
时间窗: Measured from Day 3 to Day 5
To measure the area under the background-corrected plasma nicotine concentration-time curve (AUC)
Time to the background-corrected maximum concentration (Tmax)
时间窗: Measured from Day 3 to Day 5
To measure the time to the background-corrected maximum concentration \[Tmax\]
Terminal elimination rate constant (λz)
时间窗: Measured from Day 3 to Day 5
To measure the terminal elimination rate constant (λz)
Half-life of nicotine (t1/2)
时间窗: Measured from Day 3 to Day 5
To measure the half-life of nicotine (t1/2)
次要结局
- Product consumption(Measured from Day 1 to Day 2)
- NEQ in Plasma(Measured from Day 1 to Day 2)
- NEQ in Urine(Measured from Day 1 to Day 3)
- Craving for using a tobacco or nicotine product(Measured from Day 3 to Day 5)
- Product Liking(Measured from Day 3 to Day 5)
- Nicotine Satisfaction(Measured from Day 3 to Day 5)
- Product Experience(Measured from Day 3 to Day 5)