Exploratory THS 2.1 Biomarkers of Exposure Study

Not Applicable

Completed

• Conditions: Smoking
• Interventions: Other: Conventional cigarettes (CC); Other: THS 2.1

• Registration Number: NCT01780714
• Lead Sponsor: Philip Morris Products S.A.

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.

Study Timeline

• Study Start: 2012-06
• Primary Completion: 2012-07
• Study Completion: 2012-12
• Study First Submitted: 2013-01-15
• Study First Submitted QC: 2013-01-29
• Study First Posted: 2013-01-31
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-18
• Last Update Posted: 2019-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional cigarettes (CC)	Conventional cigarettes (CC)	Smokers are continuing to smoke exclusively their usual own brand of CC, for 5 days, ad libitum, under highly controlled conditions
Tobacco Heating System 2.1 (THS 2.1)	THS 2.1	Smokers are switching to the exclusive and ad-libitum use of THS 2.1 for 5 days, under highly controlled conditions

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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
Safety monitoring	8 days + 7 days follow-up	Monitoring of adverse events, based on clinical and laboratory evaluation
Cough Visual Analog Scale (Cough VAS)	7 days	Visual Analog Scale on cough
Minnesota Withdrawal Scale-Revised (MNSWS-R)	5 days	MNWS-R questionnaire measuring subjective effects of smoking
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

Trial Locations

Locations (1)

MTZ Clinical Research Sp. z o.o.; 🇵🇱 Warsaw, Poland