Clinical trial NCT00812279: Investigate the Exposure to Selected Smoke Constituents in Smokers Switching to Distillation Based Smoking Article
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking
Keywords: Smokers with acceptable health conditions
Lead sponsor: Philip Morris Products S.A.
Sponsor class: INDUSTRY
First posted: 2008-12-22
Enrollment: 112
Sex: ALL
Minimum age (years): 23
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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)
timeFrame: 5 days
Secondary outcomes:
measure: To explore changes from baseline COHb, S-PMA, and total NNAL in the three study arms in the course of the study
timeFrame: 5 days
measure: To explore changes from baseline in the three study arms with regard to urinary excretion of biomarkers of exposure to several other smoke constituents.
timeFrame: 5 days
measure: To assess urinary excretion of nicotine and its five major nicotine metabolites in the three study arms
timeFrame: 5 days
measure: 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
timeFrame: 5 days
measure: To assess the mutagenicity potential in urine at the end of the study in the three study arms
timeFrame: 5 days
measure: To monitor blood pressure, pulse rate, electrocardiogram, clinical laboratory parameters (standard clinical biochemistry, standard haematology and urine analysis), and adverse events
timeFrame: 5 days
measure: To investigate craving and withdrawal symptoms as well as pulmonary symptoms in all three study arms by means of questionnaires
timeFrame: 5 days
measure: To investigate change in cytochrome P450 1A2 (CYP1A2) activity from D0 to D5 in the three study arms
timeFrame: 5 days
measure: To assess and compare human smoking topography (HST) in smokers before and after switching to SMAR
timeFrame: 5 days
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: MTZ Clinical Research Inc.
Study officials:
affiliation: MTZ Clinical Research Inc (Warsaw, Poland)
name: Katarzyna Jarus-Dziedzic, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ludicke F, Haziza C, Weitkunat R, Magnette J. Evaluation of Biomarkers of Exposure in Smokers Switching to a Carbon-Heated Tobacco Product: A Controlled, Randomized, Open-Label 5-Day Exposure Study. Nicotine Tob Res. 2016 Jul;18(7):1606-13. doi: 10.1093/ntr/ntw022. Epub 2016 Jan 27.