Exploratory THS 2.1 Biomarkers of Exposure Study (ZRHX-EX-01)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Philip Morris Products S.A.
ClinicalTrials.gov Identifier:
NCT01780714
First received: January 15, 2013
Last updated: January 29, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention
Smoking
Other: Conventional cigarettes (CC)
Other: THS 2.1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Philip Morris Products S.A.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Biomarkers of exposure to carbon monoxide (CO), acrolein, 1,3-butadiene, and benzene


Secondary Outcome Measures:
  • Selected secondary biomarkers of exposure to HPHCs [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    Time course of nicotine plasma concentrations and derived pharmacokinetic parameters

  • 11-dehydro-thromboxane B2 (11-DTX-B2) [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    To describe the 11-DTX-B2 levels in urine as a marker of platelet function

  • Product use and smoking topography [ Time Frame: Up to 5 days ] [ Designated as safety issue: No ]
    Monitoring of daily product use and human smoking topography

  • Safety monitoring [ Time Frame: 8 days + 7 days follow-up ] [ Designated as safety issue: Yes ]
    Monitoring of adverse events, based on clinical and laboratory evaluation

  • Cough Visual Analog Scale (Cough VAS) [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Visual Analog Scale on cough

  • Modified Cigarette Evaluation Questionnaire (MCEQ) [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    MCEQ measuring subjective effects of smoking

  • Questionnaire on Smoking Urges (brief version) (QSU-brief) [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    QSU-brief measuring subjective effects of smoking

  • Minnesota Withdrawal Scale-Revised (MNSWS-R) [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    MNWS-R questionnaire measuring subjective effects of smoking


Enrollment: 42
Study Start Date: June 2012
Study Completion Date: December 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Conventional cigarettes (CC)
Smokers are continuing to smoke exclusively their usual own brand of CC, for 5 days, ad libitum, under highly controlled conditions
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
Experimental: Tobacco Heating System 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
Other: 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

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

Ages Eligible for Study:   23 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01780714

Locations
Poland
MTZ Clinical Research Sp. z o.o.
Warsaw, Poland, 02-106
Sponsors and Collaborators
Philip Morris Products S.A.
Investigators
Principal Investigator: Katarzyna Jarus-Dziedzic, MD PhD MTZ Clinical Research Sp. z o.o., Warsaw, Poland
  More Information

No publications provided

Responsible Party: Philip Morris Products S.A.
ClinicalTrials.gov Identifier: NCT01780714     History of Changes
Other Study ID Numbers: ZRHX-EX-01
Study First Received: January 15, 2013
Last Updated: January 29, 2013
Health Authority: Poland: IEC

Keywords provided by Philip Morris Products S.A.:
smoking
cigarette
exposure
biomarker
human smoking topography (HST)
modified risk tobacco product (MRTP)
THS 2.1

Additional relevant MeSH terms:
Smoking
Habits

ClinicalTrials.gov processed this record on April 16, 2014