Real-Life Passive Exposure Assessment of IQOS

• Sponsor: Philip Morris Products S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03550989
• Collaborator: (none)
• Enrollment: 401
• Location: 1
• Actual Duration (Months): 5.3
• Patients Per Site Per Month: 75.3

Study Details

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	Phase
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: Dec 5, 2017
• Actual Primary Completion Date: Apr 30, 2018
• Actual Study Completion Date: May 16, 2018

Arms and Interventions

Arm	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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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] [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] [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] [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] [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] [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] [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] [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] [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] [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] [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

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol - Oct 10, 2017
• Statistical Analysis Plan - Jul 19, 2018

More Information

Publications

None provided.

• Responsible Party: Philip Morris Products S.A.
• ClinicalTrials.gov Identifier: NCT03550989
• Other Study ID Numbers: P1-PES-01-JP
• First Posted: Jun 11, 2018
• Last Update Posted: Aug 28, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• 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

Study Results

Participant Flow

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)	IQOS Active Users (Using IQOS)
Arm/Group Description	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.). 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. Exposure Event: Exposure Event to measure urinary BoExp to selected HPHCs representative of ETS in all participant groups, with up to 5h of exposure 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).	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) 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. Exposure Event: Exposure Event to measure urinary BoExp to selected HPHCs representative of ETS in all participant groups, with up to 5h of exposure 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).	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.) 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. Exposure Event: Exposure Event to measure urinary BoExp to selected HPHCs representative of ETS in all participant groups, with up to 5h of exposure 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).	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.) Exposure Event: Exposure Event to measure urinary BoExp to selected HPHCs representative of ETS in all participant groups, with up to 5h of exposure 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).
Period Title: Overall Study
STARTED	190	74	77	60
COMPLETED	188	73	76	60
NOT COMPLETED	2	1	1	0

Baseline Characteristics

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)	IQOS Active Users (Using IQOS)	Total
Arm/Group Description	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.).	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)	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.)	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.)	Total of all reporting groups
Overall Participants	190	74	77	60	401
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.3 (12.52)	49.9 (14.40)	43.6 (11.08)	38.8 (11.00)	44.4 (12.79)
Sex: Female, Male (Count of Participants)
Female	77 40.5%	10 13.5%	21 27.3%	13 21.7%	121 30.2%
Male	113 59.5%	64 86.5%	56 72.7%	47 78.3%	280 69.8%
Race/Ethnicity, Customized (Count of Participants)
Japanese Origin	190 100%	74 100%	77 100%	60 100%	401 100%
Region of Enrollment (participants) [Number]
Japan	190 100%	74 100%	77 100%	60 100%	401 100%

Outcome Measures

1. Primary Outcome

Title	NEQ: (Non-Exposure Event)
Description	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).
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)
Arm/Group Description	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.).	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)	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.)
Measure Participants	77	32	32
Baseline	0.03845	4.159	5.695
Final void	0.06876	5.175	6.821

2. Primary Outcome

Title	NEQ: (Exposure Event)
Description	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.
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)	IQOS Active Users (Using IQOS)
Arm/Group Description	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.).	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)	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.)	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.)
Measure Participants	113	42	45	60
Baseline	0.04078	3.051	5.277	4.683
Final void	0.06205	2.889	5.974	8.499

3. Primary Outcome

Title	Total NNAL: (Non-Exposure Event)
Description	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).
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)
Arm/Group Description	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.).	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)	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.)
Measure Participants	77	32	32
Baseline	NA	69.65	20.55
Final Void	NA	81.64	27.41

4. Primary Outcome

Title	Total NNAL: (Exposure Event)
Description	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.
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)	IQOS Active Users (Using IQOS)
Arm/Group Description	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.).	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)	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.)	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.)
Measure Participants	113	42	45	60
Baseline	NA	48.57	19.68	21.50
Final Void	NA	58.74	20.31	30.45

5. Primary Outcome

Title	Total NNN: (Non-Exposure Event)
Description	To measure Total N-nitrosonornicotine (Total NNN, a BoExp to Tobacco Specific Nitrosamines) in spot urine (expressed as concentration adjusted to creatinine).
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)
Arm/Group Description	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.).	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)	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.)
Measure Participants	77	32	32
Baseline	NA	3.945	1.493
Final Void	NA	4.008	3.093

6. Primary Outcome

Title	Total NNN: (Exposure Event)
Description	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.
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)	IQOS Active Users (Using IQOS)
Arm/Group Description	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.).	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)	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.)	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.)
Measure Participants	113	42	45	60
Baseline	NA	2.694	1.753	0.9088
Final Void	NA	3.992	2.034	2.347

7. Secondary Outcome

Title	HPMA (Non-Exposure Events)
Description	To measure 3-hydroxy-1-methylpropylmercapturic acid (HMPMA, a BoExp to Crotonaldehyde ) in spot urine (concentration adjusted for creatinine).
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)
Arm/Group Description	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.).	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)	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.)
Measure Participants	77	32	32
Baseline	103.2	318.6	133.2
Final void	232.6	307.7	211.9

8. Secondary Outcome

Title	HPMA (Exposure Events)
Description	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.
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)	IQOS Active Users (Using IQOS)
Arm/Group Description	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.).	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)	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.)	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.)
Measure Participants	113	42	45	60
Baseline	82.91	233.4	92.85	103.0
Final void	170.9	224.1	166.7	195.3

9. Secondary Outcome

Title	3-HPMA (Non-Exposure Events)
Description	To measure 3 hydroxypropylmercapturic acid (3-HPMA, a BoExp to Acrolein) in spot urine (concentration adjusted for creatinine).
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)
Arm/Group Description	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.).	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)	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.)
Measure Participants	77	32	32
Baseline	242.1	935.7	454.9
Final Void	1108	1334	1240

10. Secondary Outcome

Title	3-HPMA (Exposure Events)
Description	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.
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)	IQOS Active Users (Using IQOS)
Arm/Group Description	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.).	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)	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.)	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.)
Measure Participants	113	42	45	60
Baseline	246.6	840.6	404.4	381.1
Final Void	1982	2051	1938	1729

11. Secondary Outcome

Title	S-PMA (Non-Exposure Events)
Description	To measure S-phenylmercapturic acid (S-PMA, a BoExp to Benzene) in spot urine (concentration adjusted for creatinine).
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)
Arm/Group Description	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.).	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)	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.)
Measure Participants	77	32	32
Baseline	113.2	1441	192.6
Final Void	132.0	1023	201.3

12. Secondary Outcome

Title	S-PMA (Exposure Events)
Description	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.
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)	IQOS Active Users (Using IQOS)
Arm/Group Description	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.).	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)	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.)	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.)
Measure Participants	113	42	45	60
Baseline	123.5	735.1	151.9	195.3
Final Void	136.9	612.5	156.7	229.3

13. Secondary Outcome

Title	HEMA (Non-Exposure Events)
Description	To measure 2-hydroxyethyl mercapturic acid (HEMA, a BoExp to Ethylene Oxide) in spot urine (concentration adjusted for creatinine).
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)
Arm/Group Description	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.).	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)	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.)
Measure Participants	77	32	32
Baseline	635.1	1671	629.1
Final Void	1299	2595	1520

14. Secondary Outcome

Title	HEMA (Exposure Events)
Description	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.
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).

Outcome Measure Data

Analysis Population Description

Some participants were excluded from analysis for protocol deviations (including but not limited to, missing questionnaires, attended events but was not eligible to attend, assigned to an incorrect group, or missing samples).

Arm/Group Title	Non-Smokers	Cigarette Smokers	IQOS Passive Users (Not Using IQOS)	IQOS Active Users (Using IQOS)
Arm/Group Description	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.).	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)	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.)	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.)
Measure Participants	113	42	45	60
Baseline	651.3	1143	675.0	705.0
Final Void	1486	1967	1440	1513

15. Secondary Outcome

Title	3-Ethenylpyridine (3-EP) [µg/m^3]
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-Exposure Event	Exposure Event
Arm/Group Description	For Non-Exposure Events, Indoor Air Quality measurements were performed at the Event location for up to 3h prior to the start of the Event and for 3h after the last participant has entered the Event for 1h.	For Exposure Events, Indoor Air Quality (IAQ) measurements were performed at the Event location for up to 3h prior to start of the Exposure and for 3h after the last participant had been exposed for 1h to quantify and differentiate background exposure and to assess the impact of IQOS use on IAQ.
Measure Participants	141	260
Prior to Event	NA	NA
End of Event	NA	NA

16. Secondary Outcome

Title	Nicotine [µg/m^3]
Description	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)
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-Exposure Event	Exposure Event
Arm/Group Description	For Non-Exposure Events, Indoor Air Quality measurements were performed at the Event location for up to 3h prior to the start of the Event and for 3h after the last participant has entered the Event for 1h.	For Exposure Events, Indoor Air Quality (IAQ) measurements were performed at the Event location for up to 3h prior to start of the Exposure and for 3h after the last participant had been exposed for 1h to quantify and differentiate background exposure and to assess the impact of IQOS use on IAQ.
Measure Participants	141	260
Prior to Event	NA	NA
End of Event	NA	0.9776

17. Secondary Outcome

Title	Acetaldehyde [µg/m^3]
Description	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)
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-Exposure Event	Exposure Event
Arm/Group Description	For Non-Exposure Events, Indoor Air Quality measurements were performed at the Event location for up to 3h prior to the start of the Event and for 3h after the last participant has entered the Event for 1h.	For Exposure Events, Indoor Air Quality (IAQ) measurements were performed at the Event location for up to 3h prior to start of the Exposure and for 3h after the last participant had been exposed for 1h to quantify and differentiate background exposure and to assess the impact of IQOS use on IAQ.
Measure Participants	141	260
Prior to Event	16.52	29.20
End of Event	110	187.4

18. Secondary Outcome

Title	Acrolein [µg/m^3]
Description	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)
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-Exposure Event	Exposure Event
Arm/Group Description	For Non-Exposure Events, Indoor Air Quality measurements were performed at the Event location for up to 3h prior to the start of the Event and for 3h after the last participant has entered the Event for 1h.	For Exposure Events, Indoor Air Quality (IAQ) measurements were performed at the Event location for up to 3h prior to start of the Exposure and for 3h after the last participant had been exposed for 1h to quantify and differentiate background exposure and to assess the impact of IQOS use on IAQ.
Measure Participants	141	260
Prior to Event	0.03291	0.07646
End of Event	0.07368	0.3288

19. Secondary Outcome

Title	Crotonaldehyde [µg/m^3]
Description	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)
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-Exposure Event	Exposure Event
Arm/Group Description	For Non-Exposure Events, Indoor Air Quality measurements were performed at the Event location for up to 3h prior to the start of the Event and for 3h after the last participant has entered the Event for 1h.	For Exposure Events, Indoor Air Quality (IAQ) measurements were performed at the Event location for up to 3h prior to start of the Exposure and for 3h after the last participant had been exposed for 1h to quantify and differentiate background exposure and to assess the impact of IQOS use on IAQ.
Measure Participants	141	260
Prior to Event	0.07621	0.09775
End of Event	0.1356	0.2523

20. Secondary Outcome

Title	Formaldehyde [µg/m^3]
Description	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)
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-Exposure Event	Exposure Event
Arm/Group Description	For Non-Exposure Events, Indoor Air Quality measurements were performed at the Event location for up to 3h prior to the start of the Event and for 3h after the last participant has entered the Event for 1h.	For Exposure Events, Indoor Air Quality (IAQ) measurements were performed at the Event location for up to 3h prior to start of the Exposure and for 3h after the last participant had been exposed for 1h to quantify and differentiate background exposure and to assess the impact of IQOS use on IAQ.
Measure Participants	141	260
Prior to Event	16.60	17.15
End of Event	17.49	22.74

21. Secondary Outcome

Title	NNN [µg/m^3]
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-Exposure Event	Exposure Event
Arm/Group Description	For Non-Exposure Events, Indoor Air Quality measurements were performed at the Event location for up to 3h prior to the start of the Event and for 3h after the last participant has entered the Event for 1h.	For Exposure Events, Indoor Air Quality (IAQ) measurements were performed at the Event location for up to 3h prior to start of the Exposure and for 3h after the last participant had been exposed for 1h to quantify and differentiate background exposure and to assess the impact of IQOS use on IAQ.
Measure Participants	141	260
Prior to Event	NA	NA
End of Event	NA	NA

22. Secondary Outcome

Title	NNK [µg/m^3]
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-Exposure Event	Exposure Event
Arm/Group Description	For Non-Exposure Events, Indoor Air Quality measurements were performed at the Event location for up to 3h prior to the start of the Event and for 3h after the last participant has entered the Event for 1h.	For Exposure Events, Indoor Air Quality (IAQ) measurements were performed at the Event location for up to 3h prior to start of the Exposure and for 3h after the last participant had been exposed for 1h to quantify and differentiate background exposure and to assess the impact of IQOS use on IAQ.
Measure Participants	141	260
Prior to Event	NA	NA
End of Event	NA	NA

23. Secondary Outcome

Title	PM1 Particles [µg/m^3]
Description	Real-time measurements of PM1 suspended particles in air. (ISO Norm 18144:2003)
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-Exposure Event	Exposure Event
Arm/Group Description	For Non-Exposure Events, Indoor Air Quality measurements were performed at the Event location for up to 3h prior to the start of the Event and for 3h after the last participant has entered the Event for 1h.	For Exposure Events, Indoor Air Quality (IAQ) measurements were performed at the Event location for up to 3h prior to start of the Exposure and for 3h after the last participant had been exposed for 1h to quantify and differentiate background exposure and to assess the impact of IQOS use on IAQ.
Measure Participants	141	260
Prior to Event	1.489	1.251
End of Event	11.508	9.991

24. Secondary Outcome

Title	PM2.5 Particles [µg/m^3]
Description	Real-time measurements of PM2.5 suspended particles in air. (ISO Norm 18144:2003)
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Non-Exposure Event	Exposure Event
Arm/Group Description	For Non-Exposure Events, Indoor Air Quality measurements were performed at the Event location for up to 3h prior to the start of the Event and for 3h after the last participant has entered the Event for 1h.	For Exposure Events, Indoor Air Quality (IAQ) measurements were performed at the Event location for up to 3h prior to start of the Exposure and for 3h after the last participant had been exposed for 1h to quantify and differentiate background exposure and to assess the impact of IQOS use on IAQ.
Measure Participants	141	260
Prior to Event	1.585	1.340
End of Event	12.648	10.755

Adverse Events

Time Frame	Adverse events were collected from the signature of the ICF by each subject until the end of the study, for a duration of up to 6 weeks for each subject.
Adverse Event Reporting Description	As this study was observational by design and was conducted in a post-market setting, adverse event (AE) reporting followed the Sponsor's already established post-market Safety Surveillance Procedures for spontaneously-reported events. In case of a medical event, the study staff were advised to call the local emergency number to ensure appropriate medical treatment. Any related cost for treatment and transportation was to be borne by the Sponsor.
Arm/Group Title	Non-Smokers		Cigarette Smokers		IQOS Passive Users (Not Using IQOS)		IQOS Active Users (Using IQOS)
Arm/Group Description	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.).		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)		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.)		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.)
All Cause Mortality
	Non-Smokers		Cigarette Smokers		IQOS Passive Users (Not Using IQOS)		IQOS Active Users (Using IQOS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/190 (0%)		0/74 (0%)		0/77 (0%)		0/60 (0%)
Serious Adverse Events
	Non-Smokers		Cigarette Smokers		IQOS Passive Users (Not Using IQOS)		IQOS Active Users (Using IQOS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/190 (0%)		0/74 (0%)		0/77 (0%)		0/60 (0%)
Other (Not Including Serious) Adverse Events
	Non-Smokers		Cigarette Smokers		IQOS Passive Users (Not Using IQOS)		IQOS Active Users (Using IQOS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/190 (0%)		0/74 (0%)		0/77 (0%)		0/60 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

We confirm we have the contractual provisions in place which specify that in no event will the study site be allowed to disclose to any third party (or publicly release) any information obtained through the study without the CRO's prior written consent which in turn cannot provide such consent without Sponsor's approval unless such publication is made to satisfy regulatory requirements. The Intellectual Property rights and research results from the present study belong to the Sponsor.