Clinical trial NCT01780714: Exploratory THS 2.1 Biomarkers of Exposure Study
Official title: A Single-center, Open-label, Randomized, Controlled, 2-arm Parallel Group Study to Evaluate the Exposure to Selected Smoke Constituents in Smoking, But Otherwise Healthy Subjects Switching From Conventional Cigarettes to the Tobacco Heating System (THS) 2.1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking
Keywords: smoking
cigarette
exposure
biomarker
human smoking topography (HST)
modified risk tobacco product (MRTP)
THS 2.1
Lead sponsor: Philip Morris Products S.A.
Sponsor class: INDUSTRY
First posted: 2013-01-31
Enrollment: 42
Sex: ALL
Minimum age (years): 23
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 5 days
Secondary outcomes:
measure: Selected secondary biomarkers of exposure to HPHCs
timeFrame: 5 days
measure: CYP1A2 activity and CYP2A6 activity
timeFrame: 5 days
measure: Plasma nicotine
timeFrame: 5 days
measure: 11-dehydro-thromboxane B2 (11-DTX-B2)
timeFrame: 5 days
measure: Product use and smoking topography
timeFrame: Up to 5 days
measure: Safety monitoring
timeFrame: 8 days + 7 days follow-up
measure: Cough Visual Analog Scale (Cough VAS)
timeFrame: 7 days
measure: Modified Cigarette Evaluation Questionnaire (MCEQ)
timeFrame: 5 days
measure: Questionnaire on Smoking Urges (brief version) (QSU-brief)
timeFrame: 5 days
measure: Minnesota Withdrawal Scale-Revised (MNSWS-R)
timeFrame: 5 days
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: MTZ Clinical Research Sp. z o.o.
Study officials:
affiliation: MTZ Clinical Research Sp. z o.o., Warsaw, Poland
name: Katarzyna Jarus-Dziedzic, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ludicke F, Baker G, Magnette J, Picavet P, Weitkunat R. Reduced Exposure to Harmful and Potentially Harmful Smoke Constituents With the Tobacco Heating System 2.1. Nicotine Tob Res. 2017 Feb;19(2):168-175. doi: 10.1093/ntr/ntw164. Epub 2016 Jul 1.