Real-Life Passive Exposure Assessment of IQOS

• ClinicalTrials.gov Identifier: NCT03550989
• Recruitment Status: Completed
• First Posted: June 11, 2018
• Results First Posted: July 29, 2019
• Last Update Posted: August 28, 2019
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

Study Description

Brief Summary:

This study is a non-interventional observational study designed to assess the impact of passive exposure to IQOS environmental tobacco aerosol in Non-Smokers in a real-life restaurant setting.

Condition or disease	Intervention/treatment
Environmental Exposure	Other: Non-Exposure Event; Other: Exposure Event

Detailed Description:

The purpose of the study is to show that Non-Smokers, exposed to environmental tobacco aerosol from IQOS in a restaurant setting, do not have higher urinary levels of Biomarkers of Exposure (BoExp) to selected Harmful and Potentially Harmful Constituents (HPHCs), representative of Environmental Tobacco Smoke (ETS), compared to the urinary levels of BoExp measured in Non-Smokers before IQOS environmental tobacco aerosol exposure.

Furthermore, the impact of passive exposure to IQOS environmental tobacco aerosol on IQOS Users and Cigarette Smokers, not using any tobacco or nicotine-containing products, will be investigated. This will enable the assessment of individuals with varying levels of exposure to HPHCs and determine whether there is any measurable additional exposure related to the environmental tobacco aerosol from IQOS.

The study will also evaluate Indoor Air Quality (IAQ) through the assessment of concentrations of nicotine and selected HPHCs representative of tobacco-specific and IAQ markers in the air during exposure and non-exposure periods in a real-life restaurant setting.

Study Design

• Study Type: Observational
• Actual Enrollment: 401 participants
• Observational Model: Other
• Time Perspective: Other
• Official Title: Assessment of Passive Environmental Aerosol Exposure Through IQOS (Tobacco Heating System [THS] With Marlboro Heatsticks) in a Restaurant Setting Where IQOS Use, But Not Cigarette Smoking, is Allowed.
• Actual Study Start Date: December 5, 2017
• Actual Primary Completion Date: April 30, 2018
• Actual Study Completion Date: May 16, 2018

Groups and Cohorts

Group/Cohort	Intervention/treatment
Non-Smokers; Each participant can participate in one Non-Exposure Event and one Exposure Event only.; Abstinent for at least 12 months from the use of any nicotine and/or tobacco-containing product based on self-reporting.; Must not be exposed to tobacco or nicotine-containing products use in any other substantial way (family, partner, workplace, etc.).	Other: Non-Exposure Event; Non-Exposure event of 4h duration for the individual participants, where no use of any tobacco or nicotine-containing product is allowed, designed to establish background measurements in the absence of exposure to IQOS.; Other: Exposure Event; Exposure Event designed to measure urinary BoExp to selected HPHCs representative of ETS in all participant groups, with up to 5h of exposure to IQOS tobacco environmental aerosol for non-smokers, cigarette smokers (not using any tobacco or nicotine-containing product, including cigarettes), and IQOS passive users (not using IQOS). Additionally, this event includes up to 8h of exposure for IQOS active users (using IQOS).
Cigarette Smokers; Each participant can participate in one Non-Exposure Event and one Exposure Event only.; Used at least 100 cigarettes; Smokes cigarettes daily > 1/day; Uses IQOS less than daily; Uses less than 30 HeatSticks/month; Cigarette is > 95% of tobacco/nicotine product (all product use)	Other: Non-Exposure Event; Non-Exposure event of 4h duration for the individual participants, where no use of any tobacco or nicotine-containing product is allowed, designed to establish background measurements in the absence of exposure to IQOS.; Other: Exposure Event; Exposure Event designed to measure urinary BoExp to selected HPHCs representative of ETS in all participant groups, with up to 5h of exposure to IQOS tobacco environmental aerosol for non-smokers, cigarette smokers (not using any tobacco or nicotine-containing product, including cigarettes), and IQOS passive users (not using IQOS). Additionally, this event includes up to 8h of exposure for IQOS active users (using IQOS).
IQOS Passive Users (not using IQOS); Each participant can participate in one Non-Exposure Event and one Exposure Event only.; Used at least 100 HeatSticks; Uses IQOS daily > 1/day; Smokes a cigarette less than daily; Smokes less than 30 cigarettes/month; IQOS is > 95% of tobacco/nicotine product (all product use) - excluding other products (e-cig/Ploom/etc.)	Other: Non-Exposure Event; Non-Exposure event of 4h duration for the individual participants, where no use of any tobacco or nicotine-containing product is allowed, designed to establish background measurements in the absence of exposure to IQOS.; Other: Exposure Event; Exposure Event designed to measure urinary BoExp to selected HPHCs representative of ETS in all participant groups, with up to 5h of exposure to IQOS tobacco environmental aerosol for non-smokers, cigarette smokers (not using any tobacco or nicotine-containing product, including cigarettes), and IQOS passive users (not using IQOS). Additionally, this event includes up to 8h of exposure for IQOS active users (using IQOS).
IQOS Active Users (using IQOS); Each participant can participate in one Exposure Event only.; Used at least 100 HeatSticks; Uses IQOS daily > 1/day; Smokes a cigarette less than daily; Smokes less than 30 cigarettes/month; IQOS is > 95% of tobacco/nicotine product (all product use) - excluding other products (e-cig/Ploom/etc.)	Other: Exposure Event; Exposure Event designed to measure urinary BoExp to selected HPHCs representative of ETS in all participant groups, with up to 5h of exposure to IQOS tobacco environmental aerosol for non-smokers, cigarette smokers (not using any tobacco or nicotine-containing product, including cigarettes), and IQOS passive users (not using IQOS). Additionally, this event includes up to 8h of exposure for IQOS active users (using IQOS).

Outcome Measures

Primary Outcome Measures :

1. NEQ: (Non-Exposure Event) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure nicotine equivalents (NEQ, a biomarker of exposure to Nicotine): molar sum of free nicotine, nicotine-glucuronide, free cotinine, cotinine-glucuronide, free trans-3'-hydroxycotinine, trans-3'-hydroxycotinine-glucuronide in spot urine (expressed as concentration adjusted to creatinine).
2. NEQ: (Exposure Event) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure nicotine equivalents (NEQ, a biomarker of exposure to Nicotine): molar sum of free nicotine, nicotine-glucuronide, free cotinine, cotinine-glucuronide, free trans-3'-hydroxycotinine, trans-3'-hydroxycotinine-glucuronide in spot urine (expressed as concentration adjusted to creatinine), during exposure events where some subjects used IQOS.
3. Total NNAL: (Non-Exposure Event) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL, a BoExp to Tobacco Specific Nitrosamines) in spot urine (expressed as concentration adjusted to creatinine).
4. Total NNAL: (Exposure Event) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL, a BoExp to Tobacco Specific Nitrosamines) in spot urine (expressed as concentration adjusted to creatinine), during exposure events where some subjects used IQOS.
5. Total NNN: (Non-Exposure Event) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure Total N-nitrosonornicotine (Total NNN, a BoExp to Tobacco Specific Nitrosamines) in spot urine (expressed as concentration adjusted to creatinine).
6. Total NNN: (Exposure Event) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure Total N-nitrosonornicotine (Total NNN, a BoExp to Tobacco Specific Nitrosamines) in spot urine (expressed as concentration adjusted to creatinine) during exposure events where some subjects used IQOS.

Secondary Outcome Measures :

1. HPMA (Non-Exposure Events) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure 3-hydroxy-1-methylpropylmercapturic acid (HMPMA, a BoExp to Crotonaldehyde ) in spot urine (concentration adjusted for creatinine).
2. HPMA (Exposure Events) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure 3-hydroxy-1-methylpropylmercapturic acid (HMPMA, a BoExp to Crotonaldehyde ) in spot urine (concentration adjusted for creatinine), during exposure events where some subjects used IQOS.
3. 3-HPMA (Non-Exposure Events) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure 3 hydroxypropylmercapturic acid (3-HPMA, a BoExp to Acrolein) in spot urine (concentration adjusted for creatinine).
4. 3-HPMA (Exposure Events) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure 3 hydroxypropylmercapturic acid (3-HPMA, a BoExp to Acrolein) in spot urine (concentration adjusted for creatinine), during exposure events where some subjects used IQOS.
5. S-PMA (Non-Exposure Events) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure S-phenylmercapturic acid (S-PMA, a BoExp to Benzene) in spot urine (concentration adjusted for creatinine).
6. S-PMA (Exposure Events) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure S-phenylmercapturic acid (S-PMA, a BoExp to Benzene ) in spot urine (concentration adjusted for creatinine), during exposure events where some subjects used IQOS.
7. HEMA (Non-Exposure Events) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure 2-hydroxyethyl mercapturic acid (HEMA, a BoExp to Ethylene Oxide) in spot urine (concentration adjusted for creatinine).
8. HEMA (Exposure Events) [ Time Frame: Measured in a baseline urine sample collected before the start of the event and in a final urine sample taken prior to leaving the event (4h exposure, minimum 2h exposure). ]
   To measure 2-hydroxyethyl mercapturic acid (HEMA, a BoExp to Ethylene Oxide) in spot urine (concentration adjusted for creatinine), during exposure events where some subjects used IQOS.
9. 3-Ethenylpyridine (3-EP) [µg/m^3] [ Time Frame: Measured at baseline for up to 3h prior to start of the event, then continuously during the event until 3h after the last participant has entered the event for 1h. ]

   To measure IAQ, in real-time, through the assessment of concentrations of nicotine and select HPHCs representative of ETS in the air of the study site. (ISO Norm 18144:2003)

   Note that the measurements of 3-EP [µg/m^3] were below the limit of detection.

10. Nicotine [µg/m^3] [ Time Frame: Measured at baseline for up to 3h prior to start of the event, then continuously during the event until 3h after the last participant has entered the event for 1h. ]
    To measure IAQ, in real-time, through the assessment of concentrations of nicotine and select HPHCs representative of ETS in the air of the study site. (ISO Norm 18144:2003)
11. Acetaldehyde [µg/m^3] [ Time Frame: Measured at baseline for up to 3h prior to start of the event, then continuously during the event until 3h after the last participant has entered the event for 1h. ]
    To measure IAQ, in real-time, through the assessment of concentrations of nicotine and select HPHCs representative of ETS in the air of the study site. (ISO Norm 18144:2003)
12. Acrolein [µg/m^3] [ Time Frame: Measured at baseline for up to 3h prior to start of the event, then continuously during the event until 3h after the last participant has entered the event for 1h. ]
    To measure IAQ, in real-time, through the assessment of concentrations of nicotine and select HPHCs representative of ETS in the air of the study site. (ISO Norm 18144:2003)
13. Crotonaldehyde [µg/m^3] [ Time Frame: Measured at baseline for up to 3h prior to start of the event, then continuously during the event until 3h after the last participant has entered the event for 1h. ]
    To measure IAQ, in real-time, through the assessment of concentrations of nicotine and select HPHCs representative of ETS in the air of the study site. (ISO Norm 18144:2003)
14. Formaldehyde [µg/m^3] [ Time Frame: Measured at baseline for up to 3h prior to start of the event, then continuously during the event until 3h after the last participant has entered the event for 1h. ]
    To measure IAQ, in real-time, through the assessment of concentrations of nicotine and select HPHCs representative of ETS in the air of the study site. (ISO Norm 18144:2003)
15. NNN [µg/m^3] [ Time Frame: Measured at baseline for up to 3h prior to start of the event, then continuously during the event until 3h after the last participant has entered the event for 1h. ]

    To measure IAQ, in real-time, through the assessment of concentrations of nicotine and select HPHCs representative of ETS in the air of the study site. (ISO Norm 18144:2003)

    Note that the measurements were below the limit of detection.

16. NNK [µg/m^3] [ Time Frame: Measured at baseline for up to 3h prior to start of the event, then continuously during the event until 3h after the last participant has entered the event for 1h. ]

    To measure IAQ, in real-time, through the assessment of concentrations of nicotine and select HPHCs representative of ETS in the air of the study site. (ISO Norm 18144:2003)

    Note that the measurements of NNK [µg/m3] were below the limit of detection.

17. PM1 Particles [µg/m^3] [ Time Frame: Measured at baseline for up to 3h prior to start of the event, then continuously during the event until 3h after the last participant has entered the event for 1h. ]
    Real-time measurements of PM1 suspended particles in air. (ISO Norm 18144:2003)
18. PM2.5 Particles [µg/m^3] [ Time Frame: Measured at baseline for up to 3h prior to start of the event, then continuously during the event until 3h after the last participant has entered the event for 1h. ]
    Real-time measurements of PM2.5 suspended particles in air. (ISO Norm 18144:2003)

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Female or male Japanese IQOS Users, Cigarette smokers, or Non-Smokers.

Criteria

Inclusion Criteria:

• Participant is able to understand the information provided in the Subject Information Sheet (SIS) and Informed Consent Form (ICF) (confirmed by signing the ICF) and has signed the ICF.
• Adults legally authorized to buy tobacco products in Japan (20 years of age).
• Participant is Japanese as self-reported.
• Willing to participate in the study, comply with study procedures and has access to the Internet.
• Participant is an active IQOS User, Cigarette smoker or Non-Smoker as self-reported

Exclusion Criteria:

• Participant with a medical history of severe cardiovascular or respiratory diseases (e.g., stroke, acute cardiovascular event, pulmonary thrombosis) in the last 12 months as self-reported.
• Participant with currently active cancer or history of cancer within the last 5 years as self-reported.
• Female participant who is pregnant or breast-feeding as self-reported.
• Participant is a current or former employee of the tobacco industry or their first-degree relatives (parent and child).
• Participant is an employee of Philip Morris International (PMI), an employee of the Contract Research Organization (CRO) engaged for this study, an employee of the CRO's vendors, an employee of the restaurant/event location, or their first-degree relatives (parent or child).

Exclusion criteria specific to participants who are Non-Smokers:

• Participant lives in a household with users of tobacco or nicotine-containing products, or is exposed to the use of tobacco or nicotine-containing products at the workplace.

Contacts and Locations

Locations

Japan

Angepatio Restaurant

Shibuya-ku, Tokyo, Japan, 150-0036

Sponsors and Collaborators

Philip Morris Products S.A.

Investigators

• Study Chair: Patrick Picavet, MD; Philip Morris Products S.A.
• Principal Investigator: Takao Ohki, MD, PhD; Jikei University School of Medicine, Tokyo

  Study Documents (Full-Text)

Documents provided by Philip Morris Products S.A.:

Study Protocol  [PDF] October 10, 2017

Statistical Analysis Plan  [PDF] July 19, 2018

More Information

• Responsible Party: Philip Morris Products S.A.
• ClinicalTrials.gov Identifier: NCT03550989
• Other Study ID Numbers: P1-PES-01-JP
• First Posted: June 11, 2018
• Results First Posted: July 29, 2019
• Last Update Posted: August 28, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Philip Morris Products S.A.:

Environmental Aerosol Exposure; Environmental Tobacco Smoke; Indoor Air Quality