Smoking
Conditions
Keywords
smoking, cigarette, exposure, biomarker, human smoking topography (HST), modified risk tobacco product (MRTP), THS 2.1
Brief summary
The goal of this exploratory study is to evaluate the effect of a candidate modified risk tobacco product (MRTP), THS 2.1, on selected biomarkers of exposure to harmful and potentially harmful smoke constituents (HPHCs), compared to conventional cigarettes (CC). The subjective effects (urge to smoke and withdrawal symptoms) which are related to the use of this product will be explored. Initial information on safety and on some biological effects when using THS 2.1 will be collected. Human Smoking Topography (HST) will be explored.
Detailed description
This study intends to evaluate the levels of selected biomarkers of exposure to selected HPHC and of cytochrome P450 1A2 (CYP1A2) enzymatic activity, as compared to smokers continuing smoking CC ad libitum, after 5 days of ad libitum use. Additional parameters will be explored, such as: cytochrome P450 2A6 (CYP2A6) enzymatic activity, nicotine pharmacokinetics, product evaluation and safety, marker of platelet function, and HST. After screening, subjects will be admitted to the clinic for 9 days, including the Day of Admission, 2 days of baseline during which all subjects will continue to smoke their usual CC for a 5-day exposure after randomization. After leaving the clinic on the Day of Discharge, the subjects will be followed up for safety over a period of 7 days. All subjects will receive smoking cessation advice at screening, at Day of Admission and at Day of Discharge. This clinical study will be conducted in compliance with International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH Good Clinical Practice), the Declaration of Helsinki as amended in 2008, and the applicable regulatory requirements.
Interventions
Subjects are randomized in a 1:1 fashion to be assigned either A) continuing CC, or B) switching to THS 2.1
OTHERTHS 2.1
Subjects are randomized in a 1:1 fashion to be assigned either A) continuing CC, or B) switching to THS 2.1
Sponsors
Philip Morris Products S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
23 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject has signed an informed consent form before commencement of study procedures * Healthy Caucasian aged between 23 to 65 years * Subject is a current smoker for at least 3 years (based on self-reporting and biochemically verified), who, for the last 4 weeks, had smoked at least 10 commercially available non-mentholated CC per day, and is not planning to make a quit attempt within the next 3 months Main
Exclusion criteria
* As per Investigator judgment, the subject should not participate in the study for any reason (e.g. medical, psychiatric and/or social reason) * The subject has a medical condition requiring smoking cessation, or has a clinically relevant disease / condition which could interfere with the study participation and/or study results * The subject has participated in a clinical study within 3 months prior to the Screening Visit * Pregnant or lactating woman, and for woman of childbearing potential, absence / refusal to use an acceptable method of effective contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of carboxyhemoglobin (COHb) levels in blood, and evaluation of excretion of 3-hydroxypropyl mercapturic acid (3-HPMA), monohydroxybutenyl mercapturic acid (MHBMA), and S-phenyl mercapturic acid (S-PMA) in 24-hour urine on switching to THS 2.1 | 5 days | Biomarkers of exposure to carbon monoxide (CO), acrolein, 1,3-butadiene, and benzene |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CYP1A2 activity and CYP2A6 activity | 5 days | Evaluation of the CYP1A2 activity, as measured by the plasma caffeine molar metabolic ratio (paraxanthine / caffeine) and in CYP2A6 activity, as measured by nicotine molar metabolic ratio (3-hydroxy-cotinine / cotinine) in plasma and in urine |
| Plasma nicotine | 5 days | Time course of nicotine plasma concentrations and derived pharmacokinetic parameters |
| 11-dehydro-thromboxane B2 (11-DTX-B2) | 5 days | To describe the 11-DTX-B2 levels in urine as a marker of platelet function |
| Product use and smoking topography | Up to 5 days | Monitoring of daily product use and human smoking topography |
| Selected secondary biomarkers of exposure to HPHCs | 5 days | Evaluation of the levels of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL),1-hydroxypyrene , total N-nitrosonornicotine (NNN), 4-aminobiphenyl (4-ABP), 2- aminonaphthalene (2-NA), o-toluidine, nicotine equivalents and 2-cyanoethylmercapturic acid, biomarkers of exposure to the HPHCs 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone, NNN, 4-ABP, 2-NA, o-toluidine, nicotine and acrylonitrile, respectively, as excreted in urine. |
| Cough Visual Analog Scale (Cough VAS) | 7 days | Visual Analog Scale on cough |
| Modified Cigarette Evaluation Questionnaire (MCEQ) | 5 days | MCEQ measuring subjective effects of smoking |
| Questionnaire on Smoking Urges (brief version) (QSU-brief) | 5 days | QSU-brief measuring subjective effects of smoking |
| Minnesota Withdrawal Scale-Revised (MNSWS-R) | 5 days | MNWS-R questionnaire measuring subjective effects of smoking |
| Safety monitoring | 8 days + 7 days follow-up | Monitoring of adverse events, based on clinical and laboratory evaluation |
Countries
Poland
Outcome results
None listed