Exploratory THS 2.1 Biomarkers of Exposure Study

Smoking Clinical Trial

— ZRHX-EX-01  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01780714
• Other study ID #: ZRHX-EX-01
• Status: Completed
• Phase: N/A
• Start date: June 2012
• Est. completion date: December 2012

Study information

• Verified date: November 2019
• Source: Philip Morris Products S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: December 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 23 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Smoking

Intervention

Other:
• Conventional cigarettes (CC)
Subjects are randomized in a 1:1 fashion to be assigned either A) continuing CC, or B) switching to THS 2.1
• THS 2.1
Subjects are randomized in a 1:1 fashion to be assigned either A) continuing CC, or B) switching to THS 2.1

Locations

Country	Name	City	State
Poland	MTZ Clinical Research Sp. z o.o.	Warsaw

Sponsors (1)

Lead Sponsor	Collaborator
Philip Morris Products S.A.

Country where clinical trial is conducted

Poland, 

References & Publications (1)

Lüdicke 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Biomarkers of exposure to carbon monoxide (CO), acrolein, 1,3-butadiene, and benzene	5 days
Secondary	Selected secondary biomarkers of exposure to HPHCs	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.	5 days
Secondary	CYP1A2 activity and CYP2A6 activity	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	5 days
Secondary	Plasma nicotine	Time course of nicotine plasma concentrations and derived pharmacokinetic parameters	5 days
Secondary	11-dehydro-thromboxane B2 (11-DTX-B2)	To describe the 11-DTX-B2 levels in urine as a marker of platelet function	5 days
Secondary	Product use and smoking topography	Monitoring of daily product use and human smoking topography	Up to 5 days
Secondary	Safety monitoring	Monitoring of adverse events, based on clinical and laboratory evaluation	8 days + 7 days follow-up
Secondary	Cough Visual Analog Scale (Cough VAS)	Visual Analog Scale on cough	7 days
Secondary	Modified Cigarette Evaluation Questionnaire (MCEQ)	MCEQ measuring subjective effects of smoking	5 days
Secondary	Questionnaire on Smoking Urges (brief version) (QSU-brief)	QSU-brief measuring subjective effects of smoking	5 days
Secondary	Minnesota Withdrawal Scale-Revised (MNSWS-R)	MNWS-R questionnaire measuring subjective effects of smoking	5 days