A Controlled, Randomised, Open-label, 3-arm Parallel Single-centre Confinement Study to Investigate Exposure to Selected Smoke Constituents in Smokers Switching From Conventional Cigarettes to SMAR Cigarettes for 5 Days
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- To demonstrate a reduction in the three primary biomarkers of exposure: Carboxyhaemoglobin concentration in blood, Urinary excretion of S-phenylmercapturic acid and urinary excretion of NNAL and NNAL-glucuronides (total NNAL)
研究概览
简要总结
The overall purpose of this clinical study conducted in confinement under well-defined conditions is to obtain initial data on the levels of human body exposure to selected smoked constituents of the SMAR cigarette.
The main objective of this study is to compare the biomarkers of exposure to cigarette smoke constituents in smokers switching to SMAR and to biomarkers in smokers of conventional cigarettes (CC). The biomarkers of exposure will be measured in blood and urine samples collected from the subjects. Moreover, the biomarkers in subjects smoking conventional or SMAR cigarettes will be compared with those biomarkers in smokers who stop smoking for 5 days. The short term safety of this new product will also be evaluated.
详细描述
This is a controlled, randomised, open-label, 3-arm parallel single centre confinement study to investigate exposure to selected smoke constituents in smokers switching from CC to SMAR for 5 days.
112 eligible subjects will be randomised to the 3 study arms: SMAR, conventional cigarettes (CC) and smoking cessation (SC) in a 2:1:1 ratio.
Following the screening visit (within 4 weeks prior to the day of admission), the study will be run over an 8-day period in a confined environment, consisting of the admission day (D-2), a 2-day baseline period (D-1 and D0), and a 5-day exposure period (D1 to D5). Subjects will be discharged in the morning of D6. From the discharge of the subject, a 7-day safety follow-up period will be carried out (until D13).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 23 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Caucasian adult smokers (male and female), with acceptable health conditions, aged from 23 to 55 years who usually smoke 10 to 30 non-mentholated conventional cigarettes (with a maximum ISO tar yield of 10 mg) per day, for at least the last 5 consecutive years, will be enrolled in this study.
排除标准
- •women of childbearing potential must be excluded if:Subject is pregnant (does not have negative pregnancy tests at screening and at D-2) or breastfeeding/ subject does not agree to use an acceptable method of effective contraception: intrauterine device, intrauterine system, established use of oral/injectable/implantable/ transdermal hormonal methods, barrier methods of contraception (condoms, occlusive caps) with spermicidal foam/gel/film/suppository, vasectomised partner or true abstinence (periodic abstinence and withdrawal are not effective methods) until the end of the safety follow-up period.
研究组 & 干预措施
1. SMAR
Subjects will be allowed to smoke SMAR without any limit on consumption during the designated smoking times.
干预措施: Distillation based smoking article (SMAR cigarette) (Other)
2 Conventional cigarette (CC)
Subjects will be allowed to smoke without any limit on consumption during the designated smoking times.
干预措施: conventional cigarette (Other)
3. smoking cessation (SC)
Subjects will not be allowed to smoke any cigarettes or to use any other nicotine/tobacco-containing products during the 5 days following randomisation.
干预措施: smoking cessation (Other)
结局指标
主要结局
To demonstrate a reduction in the three primary biomarkers of exposure: Carboxyhaemoglobin concentration in blood, Urinary excretion of S-phenylmercapturic acid and urinary excretion of NNAL and NNAL-glucuronides (total NNAL)
时间窗: 5 days
次要结局
- To investigate craving and withdrawal symptoms as well as pulmonary symptoms in all three study arms by means of questionnaires(5 days)
- To explore changes from baseline in the three study arms with regard to urinary excretion of biomarkers of exposure to several other smoke constituents.(5 days)
- To assess urinary excretion of nicotine and its five major nicotine metabolites in the three study arms(5 days)
- To assess the mutagenicity potential in urine at the end of the study in the three study arms(5 days)
- To assess and compare human smoking topography (HST) in smokers before and after switching to SMAR(5 days)
- To assess nicotine and cotinine concentrations in plasma in the three study arms To compare levels of all biomarkers of exposure in the SMAR arm to those in the smoking cessation (SC) arm(5 days)
- To investigate change in cytochrome P450 1A2 (CYP1A2) activity from D0 to D5 in the three study arms(5 days)
- To explore changes from baseline COHb, S-PMA, and total NNAL in the three study arms in the course of the study(5 days)
- To monitor blood pressure, pulse rate, electrocardiogram, clinical laboratory parameters (standard clinical biochemistry, standard haematology and urine analysis), and adverse events(5 days)