Investigate the Exposure to Selected Smoke Constituents in Smokers Switching to Distillation Based Smoking Article

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

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.

Study Overview

• Status: Completed
• Conditions: Smoking
• Intervention / Treatment: Other: Distillation based smoking article (SMAR cigarette); Other: conventional cigarette; Other: smoking cessation

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).

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Warsaw, Poland, 02-106
    • MTZ Clinical Research Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1. SMAR; Subjects will be allowed to smoke SMAR without any limit on consumption during the designated smoking times.	Other: Distillation based smoking article (SMAR cigarette); Subjects randomised to the SMAR arm will be trained by the site staff on the usage of SMAR and the corresponding lighter prior to smoking the first SMAR. Subjects will be allowed to smoke SMAR without any limit on consumption during the designated smoking times but have to request each SMAR from the site staff when they wish to smoke.
Active Comparator: 2 Conventional cigarette (CC); Subjects will be allowed to smoke without any limit on consumption during the designated smoking times.	Other: conventional cigarette; Subjects randomised to the CC arm will continue to smoke their preferred CC brand during the exposure period. Subjects will be allowed to smoke without any limit on consumption during the designated smoking times but will have to request each CC from the site staff when they wish to smoke.
Active Comparator: 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.	Other: smoking cessation; Subjects will not be allowed to smoke any cigarettes or to use any other nicotine/tobacco-containing products during the 5 days following randomisation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)	5 days

Secondary Outcome Measures

Outcome Measure	Time Frame
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 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 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 assess the mutagenicity potential in urine at the end of the study in the three study arms	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
To investigate craving and withdrawal symptoms as well as pulmonary symptoms in all three study arms by means of questionnaires	5 days
To investigate change in cytochrome P450 1A2 (CYP1A2) activity from D0 to D5 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

Collaborators and Investigators

• Sponsor: Philip Morris Products S.A.
• Investigators: Principal Investigator: Katarzyna Jarus-Dziedzic, MD, MTZ Clinical Research Inc (Warsaw, Poland)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: December 19, 2008
• First Submitted That Met QC Criteria: December 19, 2008
• First Posted (Estimate): December 22, 2008

Study Record Updates

• Last Update Posted (Actual): November 7, 2019
• Last Update Submitted That Met QC Criteria: November 5, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Smokers with acceptable health conditions
• Other Study ID Numbers: YVD-CS01-EU

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No