Reduction of Exposure, Inflammation, and Oxidative Stress... | NCT05385055

NCT05385055

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

Arms/Interventions Module

Arm Groups

Label	Description	Intervention Names
Cigarette	Current cigarette smokers	Other: Cigarette smoking
THS	THS users with a minimum of 2 years of THS use	Other: THS use
SA	Former cigarette smokers with minimum of 2 years of smoking abstinence	Other: Smoking abstinence

Name	Type	Description	Arm Group Labels	Other Names
THS use	Other	N/A: No intervention was assigned.	THS
Cigarette smoking

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Carboxyhemoglobin (COHb) in Blood	Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as percentage of the total hemoglobin saturated with carbon monoxide.	Measured when subject visits study site on day 1.
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) in Urine	Concentrations of total NNAL measured in urine and expressed as concentration adjusted for creatinine (pg/mg creatinine).	Measured when subject visits study site on day 1.
White Blood Cell Total Count (WBC) in Blood	Total count in blood (10^9 cells/ L). Mean values are provided.	Measured when subject visits study site on day 1.
8-epi-Prostaglandin-F2α (8-epi-PGF2α) in Urine	Concentrations of 8-epi-PGF2α measured in urine and expressed as concentration adjusted for creatinine (pg/mg creatinine).	Measured when subject visits study site on day 1.

Secondary Outcomes

Measure	Description	Time Frame
High-Density Lipoprotein Cholesterol (HDL-C)	Concentrations of HDL-C (mmol/L) measured in serum.	Measured when subject visits study site on day 1.
Soluble Intercellular Adhesion Molecule-1 (sICAM-1)

Other Outcomes

Measure	Description	Time Frame
Neutrophil to Lymphocyte Ratio (NLR)	Calculated by dividing the number of neutrophils by number of lymphocytes from serum.	Measured when subject visits study site on day 1.
High-sensitivity C-Reactive Protein (Hs-CRP)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject is able to understand the information provided in the main ICF and has signed the main ICF.
Subject is 30-60 years old.
Subject is healthy based on ECG, spirometry, vital signs, physical examination, medical history and Investigator's assessment.

Cigarette smokers:

Has smoked ≥ 10 cigarettes/day on average (no brand restriction) over the past 2 years prior to screening.
Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 10 years.
Has not used other tobacco and nicotine products apart from cigarettes on a daily basis over the past 2 years prior to screening.
Smoking status will be verified by urinary cotinine test (≥ 200 ng/mL) and CO breath test (≥ 10 ppm (1)).

THS users:

Has used ≥ 10 HeatSticks/day on average over the past 2 years prior to screening.
Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 8 years prior to switching to THS.
Has smoked < 30 cigarettes/month and used other tobacco products or e-cigarettes < daily over the past 2 years prior to screening.
Product use will be verified by urinary cotinine test (≥ 200 ng/mL) and CO breath test (< 10 ppm).

Former cigarette smokers:

Has not smoked cigarettes or used any tobacco or nicotine-containing products on a daily basis over the past 2 years prior to screening.
Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 8 years prior to stopping smoking.
Smoking status will be verified by urinary cotinine test (< 100 ng/mL) and CO breath test (< 10 ppm).

Exclusion Criteria:

As per the judgment of the Investigator, the subject cannot participate in the study for any reason (e.g., medical, psychiatric and/or social reason). The Investigator should specifically evaluate the subject's eligibility considering COVID-19 risk factors and local situation.
The subject is legally incompetent or physically/mentally incapable of giving consent (e.g., emergency situation, under guardianship, in a social or sanitary establishment, prisoner or involuntarily incarcerated).
The subject has/had clinically relevant diseases (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, urological, immunological, pulmonary, and cardiovascular disease) or conditions that in the opinion of the investigator would jeopardize the safety of the subject or affect the validity of the study results.
The subject has abnormal findings on physical examination, ECG, vital signs, spirometry or in the medical history, deemed clinically significant by investigators.
The subject has/had within 30 days prior to screening a body temperature >37.5°C or an acute illness (e.g., upper-respiratory-tract infection, viral infection, etc.…) or the subject is confirmed or suspected active COVID-19 infection (based on the signs and symptoms observed at the time of assessment) at screening.
The subject has used any prescribed or over-the-counter systemic medication with an impact on WBC or 8-epi-PGF2α within 5 half-lives of the medication prior to enrollment in the study (please refer to Appendix B).
Subject has high blood pressure (hypertension), defined as > 139 mmHg systolic and/or > 89 mmHg diastolic or is currently treated with medication controlling high blood pressure.
The subject has (FEV1/FVC) < 0.7 and FEV1 < 80% predicted value at post-bronchodilator (BD) spirometry.
The subject has (FEV1/FVC) < 0.75 (pre-BD) and reversibility in FEV1 (that is both > 12% and > 200 mL from pre- to post-BD values).
The subject has a history of allergic reactions to salbutamol.
The subject has a body mass index (BMI) < 18.5 or ≥ 30 kg/m2.
The subject has positive alcohol and/or drug screening test results.
The subject has donated or received whole blood or blood products within 3 months prior to V1.
The subject has been previously screened for this study.
The subject is a current or former employee of the tobacco or e-cigarettes industry or of their first-degree relatives (parent, sibling, and child).
The subject is an employee of the investigational site or any other parties involved in the study or of their first-degree relatives (parent, sibling, and child).
The subject has participated in a clinical study within 3 months prior to V1.
For women only: the subject is pregnant (does have a positive pregnancy test) or breast-feeding.

Contacts/Locations Module

Name	Affiliation	Role
Christelle Haziza, PhD	Philip Morris Products S.A.	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Medical Centre Asklepii		Kyustendil		2600	Bulgaria
Medical Centre Leo Clinic EOOD

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39882959	Derived	Ansari SM, Leroy P, de La Bourdonnaye G, Pouly S, Reese L, Haziza C. Differences in biomarkers of potential harm after 2+ years of tobacco heating system use compared to cigarette smoking: a cross-sectional study. Biomarkers. 2025 Mar;30(2):178-191. doi: 10.1080/1354750X.2025.2461069. Epub 2025 Feb 19.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
FG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 7, 2022	Apr 1, 2025

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

No data available

No data is available for this block.

Concentrations of sICAM-1 (ng/mL) measured in plasma.

Concentrations of hs-CRP (nmol/L) measured in serum.

The Modified Per-Protocol Set (mPP) is a subset of the Full Analysis Set (FAS: enrolled subjects who did not screen fail and were deemed eligible based on group allocation from the tobacco and nicotine use history questionnaire) and excludes all subjects with major deviations impacting the evaluability of the primary objective, and all subjects not belonging to a complete triplet (with one current smoker, one former smoker, and one THS user) used for matching.

Arm/Group Information

ID	Title	Description
BG000	Cigarette Smokers	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
BG001	THS Users	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
BG002	Former Smokers	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00043.3± 8.17 BG00143.1± 7.65 BG00243.5± 7.91 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000119 BG001119 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Asian - Japanese

Title	Measurements
	BG000139 BG001139 BG002

BMI

Mean

Standard Deviation

kg/m²

Title

Denominators

Categories

Title	Measurements
	BG00024.3± 3.07 BG00124.5± 3.09 BG002

Average Daily Product Consumption

Count of Participants

Participants

Title

Denominators

Categories

10 to 19 cig/day or 10 to 19 heatsticks/day

Title	Measurements
	BG000203 BG001204 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Carboxyhemoglobin (COHb) in Blood

Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as percentage of the total hemoglobin saturated with carbon monoxide.

The analysis population (Modified Per-Protocol Analysis Set [mPP]) consisted of all randomized subjects, with at least one product use experience and at least one valid non-safety assessment, and excluded subjects with major deviations impacting the evaluability of the objectives. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Posted

Geometric Least Squares Mean

95% Confidence Interval

% of CO saturated hemoglobin

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Units	Counts
Participants	OG000295 OG001295 OG002294

Title

Denominators

Categories

Title	Measurements
	OG0003.07(2.92 to 3.23) OG0011.52(1.44 to 1.60) OG0021.49(1.41 to 1.57)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A generalized linear mixed model was adjusted for the matching variables (region, age [continuous], sex, self-reported average daily product consumption over the last two years of smoking) and included study site as a random effect. For co-primary endpoints (COHb, Total NNAL, WBC, 8-epi-PGF2a) we report 95% two-sided confidence intervals and one-side p-values.	t-test, 1 sided		<0.001	This endpoint is part of the four co-primary endpoints. The P-value related to Cigarette versus THS comparison is one-sided and adjusted for multiple comparison using intersection/union tests at overall alpha level of 2.5%.	Geometric Least Square Mean Ratio	0.495			2-Sided	95	0.466	0.526			The ratio of THS to Cigarette is estimated.

Primary

Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) in Urine

Concentrations of total NNAL measured in urine and expressed as concentration adjusted for creatinine (pg/mg creatinine).

Posted

Geometric Least Squares Mean

95% Confidence Interval

pg NNAL/mg creatinine

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Primary

White Blood Cell Total Count (WBC) in Blood

Total count in blood (10^9 cells/ L). Mean values are provided.

Posted

Least Squares Mean

95% Confidence Interval

10^9 cells/ L

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Primary

8-epi-Prostaglandin-F2α (8-epi-PGF2α) in Urine

Concentrations of 8-epi-PGF2α measured in urine and expressed as concentration adjusted for creatinine (pg/mg creatinine).

Posted

Geometric Least Squares Mean

95% Confidence Interval

pg/mg creatinine

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Secondary

High-Density Lipoprotein Cholesterol (HDL-C)

Concentrations of HDL-C (mmol/L) measured in serum.

Posted

Least Squares Mean

95% Confidence Interval

mmol/L

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Secondary

Soluble Intercellular Adhesion Molecule-1 (sICAM-1)

Concentrations of sICAM-1 (ng/mL) measured in plasma.

Posted

Geometric Least Squares Mean

95% Confidence Interval

ng/mL

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Secondary

11-dehydrothromboxane B2 (11-DTX-B2)

Concentrations of 11-DTX-B2 measured in urine and expressed as concentration adjusted for creatinine (pg/mg creatinine).

Posted

Geometric Least Squares Mean

95% Confidence Interval

pg/mg creatinine

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Secondary

Augmentation Index (AIx)

The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure.

Lower AIx values indicate healthier, more flexible arteries and better cardiovascular outcomes, while higher AIx values reflect greater arterial stiffness and worse outcomes.

AIx assessments were conducted using a SphygmoCor XCEL device or similar according to the manufacturer's instructions.

Posted

Least Squares Mean

95% Confidence Interval

percentage of the pulse pressure

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002

Secondary

Forced Expiratory Volume in 1 Second (FEV1) %Predicted, Post-bronchodilator (Post-BD)

FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred).

Posted

Least Squares Mean

95% Confidence Interval

percentage

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

Neutrophil to Lymphocyte Ratio (NLR)

Calculated by dividing the number of neutrophils by number of lymphocytes from serum.

Posted

Geometric Least Squares Mean

95% Confidence Interval

ratio

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

High-sensitivity C-Reactive Protein (Hs-CRP)

Concentrations of hs-CRP (nmol/L) measured in serum.

Posted

Geometric Least Squares Mean

95% Confidence Interval

nmol/L

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

Homocysteine (HCY)

Concentrations of HCY (μmol/L) measured in plasma.

Posted

Geometric Least Squares Mean

95% Confidence Interval

umol/L

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

Myeloperoxidase (MPO)

Concentrations of MPO (ng/mL) measured in plasma.

Posted

Geometric Least Squares Mean

95% Confidence Interval

ng/mL

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

Triglycerides (TG)

Concentrations of TG (mmol/L) measured in blood.

Posted

Geometric Least Squares Mean

95% Confidence Interval

mmol/L

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette Smokers	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS Users	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smokers	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

Fibrinogen

Concentrations of Fibrinogen (g/L) measured in plasma.

Posted

Geometric Least Squares Mean

95% Confidence Interval

g/L

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette Smokers	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS Users	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smokers	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

Glycated Hemoglobin (HbA1c)

HbA1c measured in whole blood (%).

Posted

Geometric Least Squares Mean

95% Confidence Interval

% (of red blood cells)

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette Smokers	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS Users	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smokers	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio Pre-bronchodilator

Measured pre-bronchodilator

Posted

Least Squares Mean

95% Confidence Interval

ratio

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette Smokers	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS Users	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smokers	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio Post Bronchodilator

Measured post bronchodilator

Posted

Mean

95% Confidence Interval

ratio

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette Smokers	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS Users	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smokers	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

Forced Expiratory Volume in 1 Second/Forced Vital Capacity (% Predicted) Pre-bronchodilator

Measured pre-bronchodilator (% predicted values).

Posted

Least Squares Mean

95% Confidence Interval

% predicted

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette Smokers	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS Users	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smokers	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

Forced Expiratory Volume in 1 Second/Forced Vital Capacity (% Predicted) Post-bronchodilator

Measured post-bronchodilator (% predicted values).

Posted

Least Squares Mean

95% Confidence Interval

% predicted

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette Smokers	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS Users	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smokers	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

Nicotine Equivalents (NEQ) in Urine (Expressed as Concentration Adjusted to Creatinine)

NEQ measured in urine and expressed as concentration adjusted for creatinine.

Posted

Geometric Least Squares Mean

95% Confidence Interval

mg/g creatinine

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette Smokers	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS Users	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smokers	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Other Pre-specified

2-Cyanoethyl Mercapturic Acid N-Acetyl-S-(2-cyanoethyl)-L-cysteine (2CyEMA)

2CyEMA measured in urine and expressed as concentration adjusted to creatinine.

Posted

Geometric Least Squares Mean

95% Confidence Interval

ng/mg creatinine

Measured when subject visits study site on day 1.

ID	Title	Description
OG000	Cigarette Smokers	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.
OG001	THS Users	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.
OG002	Former Smokers	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (At Risk)
EG000	Cigarette	Current cigarette smokers Cigarette smoking: N/A: No intervention was assigned.	322	322	322
EG001	THS User	THS users with a minimum of 2 years of THS use THS use: N/A: No intervention was assigned.	329	329	329
EG002	Former Smoker	Former cigarette smokers with minimum of 2 years of smoking abstinence Smoking abstinence: N/A: No intervention was assigned.	323	323	323

ID	Term
D007249	Inflammation
D012907	Smoking

Units	Counts
Participants	OG000294 OG001296 OG002296

Units	Counts
Participants	OG000294 OG001296 OG002296

Units	Counts
Participants	OG000293 OG001295 OG002295

Units	Counts
Participants	OG000296 OG001296 OG002296

Units	Counts
Participants	OG000283 OG001285 OG002286

Units	Counts
Participants	OG000296 OG001296 OG002296

Units	Counts
Participants	OG000296 OG001296 OG002296

Units	Counts
Participants	OG000296 OG001296 OG002296

Units	Counts
Participants	OG000296 OG001296 OG002296

Units	Counts
Participants	OG000289 OG001296 OG002294

Units	Counts
Participants	OG000294 OG001296 OG002296

ID	Term
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D001519	Behavior