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Completed

NCT Number: NCT01780714

Exploratory THS 2.1 Biomarkers of Exposure Study

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.

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Key information

Conditions

Smoking Behavior

Age range

23 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

MTZ Clinical Research Sp. z o.o.

Warsaw, 02-106, Poland

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Conventional cigarettes (CC)

Other

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

Other

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

Primary outcomes

  1. 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

    Time frame: 5 days

    Biomarkers of exposure to carbon monoxide (CO), acrolein, 1,3-butadiene, and benzene

Secondary outcomes

  1. Selected secondary biomarkers of exposure to HPHCs

    Time frame: 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.

  2. CYP1A2 activity and CYP2A6 activity

    Time frame: 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

  3. Plasma nicotine

    Time frame: 5 days

    Time course of nicotine plasma concentrations and derived pharmacokinetic parameters

  4. 11-dehydro-thromboxane B2 (11-DTX-B2)

    Time frame: 5 days

    To describe the 11-DTX-B2 levels in urine as a marker of platelet function

  5. Product use and smoking topography

    Time frame: Up to 5 days

    Monitoring of daily product use and human smoking topography

  6. Safety monitoring

    Time frame: 8 days + 7 days follow-up

    Monitoring of adverse events, based on clinical and laboratory evaluation

  7. Cough Visual Analog Scale (Cough VAS)

    Time frame: 7 days

    Visual Analog Scale on cough

  8. Modified Cigarette Evaluation Questionnaire (MCEQ)

    Time frame: 5 days

    MCEQ measuring subjective effects of smoking

  9. Questionnaire on Smoking Urges (brief version) (QSU-brief)

    Time frame: 5 days

    QSU-brief measuring subjective effects of smoking

  10. Minnesota Withdrawal Scale-Revised (MNSWS-R)

    Time frame: 5 days

    MNWS-R questionnaire measuring subjective effects of smoking

Sponsors and collaborators

Lead sponsor

Philip Morris Products S.A.

Industry

Registry information

Official study 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

Acronym: ZRHX-EX-01

Important dates

Study start
2012
Primary completion
2012
Study completion
2012
First posted
Jan 31, 2013
Registry last updated
Nov 20, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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