Trial Outcomes & Findings for Effect of Switching From Cigarette Smoking to the Use of IQOS on Periodontitis Treatment Outcome (NCT NCT03364751)

NCT ID: NCT03364751

Last Updated: 2023-01-30

Results Overview

Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Mean Periodontal PD change from baseline will be measured in all sites with initial PD ≥ 4 mm, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 179 participants
• Primary outcome timeframe: At 6 months
• Results posted on: 2023-01-30

Participant Flow

179 subjects were enrolled in the study. 172 subjects were randomized to the IQOS arm (n=87) or to the cigarette arm (n=85). The analysis was performed according to subjects' exposure (Product Use Category, i.e., IQOS; Cigarette; Dual use; or Other) over the study period as detailed in the "Arm/Group" (Reporting Groups) table.

Participant milestones

Measure	IQOS IQOS Product Use Category: Subjects using over 30 HeatSticks, but less than 30 cigarettes monthly were classified as "IQOS" users (based on self-report).	Cigarette Cigarette Product Use Category: Monthly users of less than 30 HeatSticks, but over 30 cigarettes were classified as "Cigarette" users (based on self-report).	Dual User Dual User Product Use Category: Users of over 30 HeatSticks and over 30 cigarettes per month were classified as "Dual User" (based on self-report).	Other Other Product Use Category: All other use patterns were classified as "Other" (based on self-report).
Overall Study STARTED	70	84	17	1
Overall Study COMPLETED	69	83	17	1
Overall Study NOT COMPLETED	1	1	0	0

Reasons for withdrawal

Measure	IQOS IQOS Product Use Category: Subjects using over 30 HeatSticks, but less than 30 cigarettes monthly were classified as "IQOS" users (based on self-report).	Cigarette Cigarette Product Use Category: Monthly users of less than 30 HeatSticks, but over 30 cigarettes were classified as "Cigarette" users (based on self-report).	Dual User Dual User Product Use Category: Users of over 30 HeatSticks and over 30 cigarettes per month were classified as "Dual User" (based on self-report).	Other Other Product Use Category: All other use patterns were classified as "Other" (based on self-report).
Overall Study Withdrawal by Subject	1	0	0	0
Overall Study Lost to Follow-up	0	1	0	0

Baseline Characteristics

Effect of Switching From Cigarette Smoking to the Use of IQOS on Periodontitis Treatment Outcome

Baseline characteristics by cohort

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category	Total n=172 Participants Total of all reporting groups
Age, Continuous	48.1 years n=5 Participants	46.5 years n=7 Participants	54.4 years n=5 Participants	54.0 years n=4 Participants	48.0 years n=21 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	17 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	33 Participants n=21 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	67 Participants n=7 Participants	14 Participants n=5 Participants	1 Participants n=4 Participants	139 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	70 Participants n=5 Participants	84 Participants n=7 Participants	17 Participants n=5 Participants	1 Participants n=4 Participants	172 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment Japan	70 participants n=5 Participants	84 participants n=7 Participants	17 participants n=5 Participants	1 participants n=4 Participants	172 participants n=21 Participants
Nationality Japanese	70 Participants n=5 Participants	84 Participants n=7 Participants	17 Participants n=5 Participants	1 Participants n=4 Participants	172 Participants n=21 Participants
Nationality Non-Japanese	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: At 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements). The "Other" reporting group, which included one subject, was not included in this analysis.

Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Mean Periodontal PD change from baseline will be measured in all sites with initial PD ≥ 4 mm, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other Other Product Use Category
Periodontal Pocket Depth (PD) Change From Baseline at 6 Months	-1.046 millimeters Interval -1.194 to -0.898	-1.114 millimeters Interval -1.258 to -0.97	-1.177 millimeters Interval -1.399 to -0.956	—

SECONDARY outcome

Timeframe: At 3 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements). The "Other" reporting group, which included one subject, was not included in this analysis.

Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Mean Periodontal PD change from baseline will be measured in all sites with initial PD ≥ 4 mm, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other Other Product Use Category
Periodontal Pocket Depth (PD) Change Over Time. (Mean PD in All Subjects With Initial PD ≥ 4 mm)	-0.972 millimeters Interval -1.12 to -0.824	-1.016 millimeters Interval -1.158 to -0.873	-1.035 millimeters Interval -1.257 to -0.814	—

SECONDARY outcome

Timeframe: At 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements). The "Other" reporting group, which included one subject, was not included in this analysis.

Clinical attachment level (CAL) is the measured distance from cementoenamel junction (CEJ) to the bottom of pocket using a periodontal probe. Mean CAL change from baseline will be measured in sites with initial PD ≥ 4 mm, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=83 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other Other Product Use Category
Clinical Attachment Level (CAL) Change Over Time (Mean CAL in All Subjects With Initial PD ≥ 4 mm) Month 3: Change from Baseline	-0.820 millimeters Interval -0.98 to -0.66	-0.889 millimeters Interval -1.043 to -0.736	-0.865 millimeters Interval -1.122 to -0.608	—
Clinical Attachment Level (CAL) Change Over Time (Mean CAL in All Subjects With Initial PD ≥ 4 mm) Month 6: Change from Baseline	-0.903 millimeters Interval -1.064 to -0.743	-0.995 millimeters Interval -1.15 to -0.84	-1.100 millimeters Interval -1.357 to -0.843	—

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Mean Periodontal PD change from baseline will be measured in all sites with initial PD ≥ 4 mm, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Periodontal Pocket Depth (PD) Change Over Time. (Mean PD in All Subjects With Initial PD ≥ 4 mm) - Descriptive Statistics Baseline	4.45 millimeters Interval 4.34 to 4.56	4.43 millimeters Interval 4.35 to 4.51	4.34 millimeters Interval 4.25 to 4.44	4.07 millimeters
Periodontal Pocket Depth (PD) Change Over Time. (Mean PD in All Subjects With Initial PD ≥ 4 mm) - Descriptive Statistics Month 3	3.44 millimeters Interval 3.28 to 3.6	3.47 millimeters Interval 3.34 to 3.6	4.34 millimeters Interval 4.25 to 4.44	3.04 millimeters
Periodontal Pocket Depth (PD) Change Over Time. (Mean PD in All Subjects With Initial PD ≥ 4 mm) - Descriptive Statistics Month 6	3.36 millimeters Interval 3.2 to 3.52	3.37 millimeters Interval 3.23 to 3.51	3.29 millimeters Interval 3.03 to 3.54	3.09 millimeters

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Clinical attachment level (CAL) is the measured distance from cementoenamel junction (CEJ) to the bottom of pocket using a periodontal probe. Mean CAL change from baseline will be measured in sites with initial PD ≥ 4 mm, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Clinical Attachment Level (CAL) Change Over Time (Mean CAL in All Subjects With Initial PD ≥ 4 mm) - Descriptive Statistics Baseline	4.65 millimeters Interval 4.45 to 4.84	4.64 millimeters Interval 4.45 to 4.82	4.60 millimeters Interval 4.36 to 4.85	4.13 millimeters
Clinical Attachment Level (CAL) Change Over Time (Mean CAL in All Subjects With Initial PD ≥ 4 mm) - Descriptive Statistics Month 3	3.82 millimeters Interval 3.57 to 4.07	3.79 millimeters Interval 3.57 to 4.01	3.87 millimeters Interval 3.48 to 4.26	3.20 millimeters
Clinical Attachment Level (CAL) Change Over Time (Mean CAL in All Subjects With Initial PD ≥ 4 mm) - Descriptive Statistics Month 6	3.74 millimeters Interval 3.48 to 3.99	3.69 millimeters Interval 3.46 to 3.91	3.64 millimeters Interval 3.24 to 4.04	3.21 millimeters

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Change in mean full-mouth PD will be measured, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Full-mouth Periodontal PD Change Over Time. Baseline	3.15 millimeters Interval 3.02 to 3.29	3.20 millimeters Interval 3.09 to 3.31	2.99 millimeters Interval 2.8 to 3.17	2.92 millimeters
Full-mouth Periodontal PD Change Over Time. Month 3	2.70 millimeters Interval 2.59 to 2.81	2.78 millimeters Interval 2.67 to 2.88	2.69 millimeters Interval 2.5 to 2.88	2.57 millimeters
Full-mouth Periodontal PD Change Over Time. Month 6	2.70 millimeters Interval 2.58 to 2.82	2.72 millimeters Interval 2.6 to 2.84	2.62 millimeters Interval 2.39 to 2.84	2.55 millimeters

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Clinical attachment level (CAL) is the measured distance from cementoenamel junction (CEJ) to the bottom of pocket using a periodontal probe. Change in mean full-mouth CAL will be measured, following mechanical periodontal therapy, in patients who switch to IQOS use compared to those who continue cigarette smoking.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Full-mouth Clinical Attachment Level (CAL) Over Time. Baseline	3.48 millimeters Interval 3.26 to 3.69	3.52 millimeters Interval 3.34 to 3.71	3.34 millimeters Interval 3.0 to 3.69	2.99 millimeters
Full-mouth Clinical Attachment Level (CAL) Over Time. Month 3	3.10 millimeters Interval 2.88 to 3.31	3.13 millimeters Interval 2.93 to 3.32	3.15 millimeters Interval 2.75 to 3.54	2.70 millimeters
Full-mouth Clinical Attachment Level (CAL) Over Time. Month 6	3.10 millimeters Interval 2.86 to 3.33	3.09 millimeters Interval 2.89 to 3.29	2.97 millimeters Interval 2.59 to 3.36	2.70 millimeters

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Mean PD change will be measured in sites with initial PD < 4 mm, and with initial PD of 4 mm to <5 mm, 5 mm to < 6 mm, 6 mm to < 7 mm and ≥ 7 mm.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Peridontal PD Reduction. 4mm-5mm (Month 3: Change from Baseline)	-0.8 millimeters Interval -0.9 to -0.7	-0.8 millimeters Interval -0.9 to -0.7	-0.8 millimeters Interval -0.9 to -0.6	-1.0 millimeters
Peridontal PD Reduction. <4mm (Baseline)	2.5 millimeters Interval 2.5 to 2.6	2.6 millimeters Interval 2.5 to 2.6	2.5 millimeters Interval 2.4 to 2.6	2.6 millimeters
Peridontal PD Reduction. <4mm (Month 3: Change from Baseline)	-0.2 millimeters Interval -0.3 to -0.1	-0.2 millimeters Interval -0.2 to -0.1	-0.1 millimeters Interval -0.2 to 0.0	-0.1 millimeters
Peridontal PD Reduction. <4mm (Month 6: Change from Baseline)	-0.2 millimeters Interval -0.3 to -0.1	-0.2 millimeters Interval -0.3 to -0.2	-0.1 millimeters Interval -0.3 to 0.0	-0.1 millimeters
Peridontal PD Reduction. 4mm-5mm (Baseline)	4.0 millimeters Interval 4.0 to 4.0	4.0 millimeters Interval 4.0 to 4.0	4.0 millimeters Interval 4.0 to 4.0	4.0 millimeters
Peridontal PD Reduction. 4mm-5mm (Month 6: Change from Baseline)	-0.9 millimeters Interval -1.0 to -0.8	-0.9 millimeters Interval -1.0 to -0.8	-0.8 millimeters Interval -1.1 to -0.6	-0.9 millimeters
Peridontal PD Reduction. 5mm-6mm (Baseline)	5.0 millimeters Interval 5.0 to 5.0	5.0 millimeters Interval 5.0 to 5.0	5.0 millimeters Interval 5.0 to 5.0	5.0 millimeters
Peridontal PD Reduction. 5mm-6mm (Month 3: Change from Baseline)	-1.2 millimeters Interval -1.3 to -1.0	-1.1 millimeters Interval -1.2 to -0.9	-1.0 millimeters Interval -1.3 to -0.7	-1.8 millimeters
Peridontal PD Reduction. 5mm-6mm (Month 6: Change from Baseline)	-1.2 millimeters Interval -1.4 to -1.0	-1.2 millimeters Interval -1.4 to -1.1	-1.2 millimeters Interval -1.6 to -0.9	-2.0 millimeters
Peridontal PD Reduction. 6mm-7mm (Baseline)	6.0 millimeters Interval 6.0 to 6.0	6.0 millimeters Interval 6.0 to 6.0	6.0 millimeters Interval 6.0 to 6.0	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.
Peridontal PD Reduction. 6mm-7mm (Month 3: Change from Baseline)	-1.3 millimeters Interval -1.6 to -1.0	-1.2 millimeters Interval -1.4 to -0.9	-1.4 millimeters Interval -2.0 to -0.8	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.
Peridontal PD Reduction. 6mm-7mm (Month 6: Change from Baseline)	-1.5 millimeters Interval -1.8 to -1.3	-1.4 millimeters Interval -1.6 to -1.2	-1.8 millimeters Interval -2.3 to -1.3	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.
Peridontal PD Reduction. ≥7mm (Baseline)	7.6 millimeters Interval 7.3 to 7.9	7.5 millimeters Interval 7.3 to 7.6	8.4 millimeters Interval 6.7 to 10.1	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.
Peridontal PD Reduction. ≥7mm (Month 3: Change from Baseline)	-2.1 millimeters Interval -2.5 to -1.6	-1.6 millimeters Interval -2.0 to -1.1	-2.5 millimeters Interval -3.6 to -1.3	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.
Peridontal PD Reduction. ≥7mm (Month 6: Change from Baseline)	-2.3 millimeters Interval -2.9 to -1.7	-1.7 millimeters Interval -2.1 to -1.3	-2.3 millimeters Interval -3.4 to -1.3	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Clinical attachment level (CAL) is the measured distance from cementoenamel junction (CEJ) to the bottom of pocket using a periodontal probe. Mean CAL change will be measured in sites with initial PD < 4 mm, and with initial PD of 4 mm to <5 mm, 5 mm to < 6 mm, 6 mm to < 7 mm and ≥ 7 mm.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Clinical Attachment Level Improvement <4mm (Baseline)	3.0 millimeters Interval 2.8 to 3.1	3.0 millimeters Interval 2.8 to 3.1	2.9 millimeters Interval 2.6 to 3.3	2.6 millimeters
Clinical Attachment Level Improvement <4mm (Month 3: Change from Baseline)	-0.2 millimeters Interval -0.3 to -0.1	-0.2 millimeters Interval -0.2 to -0.1	0.0 millimeters Interval -0.2 to 0.1	-0.1 millimeters
Clinical Attachment Level Improvement <4mm (Month 6: Change from Baseline)	-0.2 millimeters Interval -0.3 to 0.0	-0.2 millimeters Interval -0.3 to -0.1	-0.2 millimeters Interval -0.4 to 0.0	-0.1 millimeters
Clinical Attachment Level Improvement 4mm-5mm (Baseline)	4.2 millimeters Interval 4.1 to 4.4	4.2 millimeters Interval 4.1 to 4.4	4.3 millimeters Interval 4.1 to 4.6	4.1 millimeters
Clinical Attachment Level Improvement 4mm-5mm (Month 3: Change from Baseline)	-0.7 millimeters Interval -0.8 to -0.6	-0.7 millimeters Interval -0.8 to -0.6	-0.6 millimeters Interval -0.8 to -0.4	-0.9 millimeters
Clinical Attachment Level Improvement 4mm-5mm (Month 6: Change from Baseline)	-0.8 millimeters Interval -0.9 to -0.6	-0.8 millimeters Interval -0.9 to -0.7	-0.8 millimeters Interval -1.0 to -0.5	-0.9 millimeters
Clinical Attachment Level Improvement 5mm-6mm (Baseline)	5.2 millimeters Interval 5.0 to 5.3	5.2 millimeters Interval 5.0 to 5.3	5.2 millimeters Interval 5.1 to 5.4	5.0 millimeters
Clinical Attachment Level Improvement 5mm-6mm (Month 3: Change from Baseline)	-0.9 millimeters Interval -1.1 to -0.8	-1.0 millimeters Interval -1.1 to -0.8	-0.8 millimeters Interval -1.1 to -0.4	-1.2 millimeters
Clinical Attachment Level Improvement 5mm-6mm (Month 6: Change from Baseline)	-1.0 millimeters Interval -1.2 to -0.8	-1.1 millimeters Interval -1.3 to -0.9	-1.2 millimeters Interval -1.6 to -0.7	-1.8 millimeters
Clinical Attachment Level Improvement 6mm-7mm (Baseline)	6.2 millimeters Interval 6.0 to 6.5	6.3 millimeters Interval 6.1 to 6.5	6.3 millimeters Interval 6.0 to 6.6	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.
Clinical Attachment Level Improvement 6mm-7mm (Month 3: Change from Baseline)	-1.0 millimeters Interval -1.4 to -0.7	-1.0 millimeters Interval -1.3 to -0.7	-1.2 millimeters Interval -1.9 to -0.4	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.
Clinical Attachment Level Improvement 6mm-7mm (Month 6: Change from Baseline)	-1.3 millimeters Interval -1.6 to -0.9	-1.3 millimeters Interval -1.5 to -1.0	-1.7 millimeters Interval -2.2 to -1.2	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.
Clinical Attachment Level Improvement ≥7mm (Baseline)	7.5 millimeters Interval 6.9 to 8.1	7.9 millimeters Interval 7.6 to 8.2	8.8 millimeters Interval 6.4 to 11.2	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.
Clinical Attachment Level Improvement ≥7mm (Month 3: Change from Baseline)	-1.3 millimeters Interval -1.9 to -0.8	-1.7 millimeters Interval -2.1 to -1.3	-1.6 millimeters Interval -3.3 to 0.1	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.
Clinical Attachment Level Improvement ≥7mm (Month 6: Change from Baseline)	-1.6 millimeters Interval -2.2 to -0.9	-1.9 millimeters Interval -2.2 to -1.5	-2.0 millimeters Interval -4.0 to 0.1	NA millimeters The sole subject in this use category did not have any sites with a PD ≥6mm.

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Pocket depth (PD) is the distance from the gingival margin to which a probe penetrates into the pocket. Any change will be recorded in the number of periodontally diseased sites with Pocket Depth (PD) < 4 mm, with PD 4 mm to < 5mm, with PD 5 mm to < 6 mm , with PD 6 mm to < 7 mm and with PD ≥ 7 mm. PD is the distance from the gingival margin to which a probe penetrates into the pocket.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Number of Periodontally Diseased Sites. <4mm: Baseline	7688 Number of sites	9194 Number of sites	1911 Number of sites	127 Number of sites
Number of Periodontally Diseased Sites. <4mm: Month 3	9332 Number of sites	11146 Number of sites	2181 Number of sites	154 Number of sites
Number of Periodontally Diseased Sites. <4mm: Month 6	9241 Number of sites	11199 Number of sites	2227 Number of sites	159 Number of sites
Number of Periodontally Diseased Sites. 4mm - 5mm: Baseline	2067 Number of sites	2571 Number of sites	469 Number of sites	37 Number of sites
Number of Periodontally Diseased Sites. 4mm - 5mm: Month 3	1037 Number of sites	1393 Number of sites	261 Number of sites	14 Number of sites
Number of Periodontally Diseased Sites. 4mm - 5mm: Month 6	934 Number of sites	1241 Number of sites	259 Number of sites	8 Number of sites
Number of Periodontally Diseased Sites. 5mm - 6mm: Baseline	724 Number of sites	1042 Number of sites	136 Number of sites	4 Number of sites
Number of Periodontally Diseased Sites. 5mm - 6mm: Month 3	366 Number of sites	483 Number of sites	102 Number of sites	0 Number of sites
Number of Periodontally Diseased Sites. 5mm - 6mm: Month 6	333 Number of sites	426 Number of sites	76 Number of sites	1 Number of sites
Number of Periodontally Diseased Sites. 6mm - 7mm: Baseline	291 Number of sites	333 Number of sites	55 Number of sites	0 Number of sites
Number of Periodontally Diseased Sites. 6mm - 7mm: Month 3	151 Number of sites	238 Number of sites	31 Number of sites	0 Number of sites
Number of Periodontally Diseased Sites. 6mm - 7mm: Month 6	189 Number of sites	219 Number of sites	23 Number of sites	0 Number of sites
Number of Periodontally Diseased Sites. ≥7mm: Baseline	220 Number of sites	222 Number of sites	15 Number of sites	0 Number of sites
Number of Periodontally Diseased Sites. ≥7mm: Month 3	124 Number of sites	113 Number of sites	10 Number of sites	0 Number of sites
Number of Periodontally Diseased Sites. ≥7mm: Month 6	126 Number of sites	120 Number of sites	7 Number of sites	0 Number of sites
Number of Periodontally Diseased Sites. Missing/Not done: Baseline	26 Number of sites	12 Number of sites	0 Number of sites	0 Number of sites
Number of Periodontally Diseased Sites. Missing/Not done: Month 3	6 Number of sites	1 Number of sites	1 Number of sites	0 Number of sites
Number of Periodontally Diseased Sites. Missing/Not done: Month 6	7 Number of sites	1 Number of sites	0 Number of sites	0 Number of sites

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Gingival inflammation will be measured by calculating the gingival index (GI) score for each target tooth.

The gingival index (GI) scores each site on a 0 to 3 scale, with 0 being normal and 3 being severe inflammation characterized by edema, redness, swelling, and spontaneous bleeding.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Gingival Inflammation Baseline	1.46 Gingival Index (GI) Interval 1.35 to 1.57	1.48 Gingival Index (GI) Interval 1.4 to 1.56	1.46 Gingival Index (GI) Interval 1.28 to 1.64	1.38 Gingival Index (GI)
Gingival Inflammation Month 3	1.06 Gingival Index (GI) Interval 0.93 to 1.2	1.08 Gingival Index (GI) Interval 0.97 to 1.19	1.22 Gingival Index (GI) Interval 1.01 to 1.44	0.5 Gingival Index (GI)
Gingival Inflammation Month 3: Change from Baseline	-0.40 Gingival Index (GI) Interval -0.52 to -0.28	-0.40 Gingival Index (GI) Interval -0.51 to -0.29	-0.24 Gingival Index (GI) Interval -0.44 to -0.03	-0.88 Gingival Index (GI)
Gingival Inflammation Month 6	1.03 Gingival Index (GI) Interval 0.9 to 1.17	1.04 Gingival Index (GI) Interval 0.93 to 1.15	1.05 Gingival Index (GI) Interval 0.87 to 1.23	1.38 Gingival Index (GI)
Gingival Inflammation Month 6: Change from Baseline	-0.43 Gingival Index (GI) Interval -0.55 to -0.3	-0.44 Gingival Index (GI) Interval -0.56 to -0.31	-0.41 Gingival Index (GI) Interval -0.67 to -0.15	0.00 Gingival Index (GI)

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Tooth mobility will be graded according to Miller's mobility index (MMI), which is the most widely accepted method for routine clinical examinations of tooth mobility. The tooth is held between the metallic handles of two instruments and moved in the buccolingual or buccopalatal direction, and the moved distance is visually estimated by the person conducting the examination.

Grade 0: Physiologic movement within 0.2 mm; Grade 1: Slight mobility, tooth can be moved 0.2 - 1 mm labiolingually; Grade 2: Moderate mobility, tooth can be moved 1 - 2 mm labiolingually or mesiodistally; Grade 3: Severe mobility, tooth can be moved more than 2 mm labiolingually or mesiodistally, or ability to depress the tooth in a vertical direction.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Tooth Mobility Baseline	0.18 MMI Interval 0.11 to 0.24	0.19 MMI Interval 0.12 to 0.26	0.23 MMI Interval 0.06 to 0.4	0 MMI
Tooth Mobility Month 3	0.17 MMI Interval 0.1 to 0.24	0.16 MMI Interval 0.09 to 0.22	0.19 MMI Interval 0.03 to 0.34	0 MMI
Tooth Mobility Month 3: Change from Baseline	-0.01 MMI Interval -0.03 to 0.02	-0.03 MMI Interval -0.06 to -0.01	-0.04 MMI Interval -0.12 to 0.04	0.00 MMI
Tooth Mobility Month 6	0.18 MMI Interval 0.1 to 0.26	0.17 MMI Interval 0.09 to 0.24	0.16 MMI Interval 0.04 to 0.27	0 MMI
Tooth Mobility Month 6: Change from Baseline	0.00 MMI Interval -0.04 to 0.04	-0.02 MMI Interval -0.05 to 0.01	-0.07 MMI Interval -0.15 to 0.0	0.00 MMI

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Plaque will be measured using the plaque control record (PCR) percentage.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Presence of Plaque on Tooth Surfaces in Full Mouth Month 6: Change from Baseline	-13.27 Plaque Control Record % Interval -18.14 to -8.41	-11.22 Plaque Control Record % Interval -14.72 to -7.71	-7.89 Plaque Control Record % Interval -17.75 to 1.98	-19.64 Plaque Control Record %
Presence of Plaque on Tooth Surfaces in Full Mouth Baseline	62.07 Plaque Control Record % Interval 57.68 to 66.46	62.48 Plaque Control Record % Interval 57.92 to 67.03	55.81 Plaque Control Record % Interval 44.62 to 67.99	77.68 Plaque Control Record %
Presence of Plaque on Tooth Surfaces in Full Mouth Month 3	48.03 Plaque Control Record % Interval 43.08 to 52.97	50.14 Plaque Control Record % Interval 45.66 to 54.62	44.56 Plaque Control Record % Interval 34.08 to 55.04	60.71 Plaque Control Record %
Presence of Plaque on Tooth Surfaces in Full Mouth Month 3: Change from Baseline	-14.27 Plaque Control Record % Interval -19.04 to -9.49	-12.34 Plaque Control Record % Interval -15.7 to -8.99	-11.25 Plaque Control Record % Interval -21.45 to -1.05	-16.96 Plaque Control Record %
Presence of Plaque on Tooth Surfaces in Full Mouth Month 6	49.60 Plaque Control Record % Interval 44.24 to 54.96	51.55 Plaque Control Record % Interval 47.2 to 55.9	47.92 Plaque Control Record % Interval 37.57 to 58.28	58.04 Plaque Control Record %

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

Gum inflammation was measured using percentage of teeth bleeding on probing (BOP).

BOP in full mouth was measured to assess inflammatory status in the pocket and was assessed as YES or NO of bleeding at 6 sites per tooth. Gently probing (approximately 20 g pressure), the bleeding site within 30 seconds was assessed as YES.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Inflammatory Status in Periodontal Pockets Baseline	41.25 BOP % Interval 35.94 to 46.56	42.93 BOP % Interval 38.33 to 47.52	30.80 BOP % Interval 23.96 to 37.65	48.81 BOP %
Inflammatory Status in Periodontal Pockets Month 3	26.68 BOP % Interval 22.3 to 31.06	24.21 BOP % Interval 20.7 to 27.71	19.03 BOP % Interval 15.49 to 22.56	53.57 BOP %
Inflammatory Status in Periodontal Pockets Month 3: Change from Baseline	-14.57 BOP % Interval -19.03 to -10.11	-18.72 BOP % Interval -21.84 to -15.6	-11.78 BOP % Interval -16.48 to -7.07	4.76 BOP %
Inflammatory Status in Periodontal Pockets Month 6	26.90 BOP % Interval 22.7 to 31.09	23.80 BOP % Interval 20.1 to 27.5	19.80 BOP % Interval 13.33 to 26.28	38.10 BOP %
Inflammatory Status in Periodontal Pockets Month 6: Change from Baseline	-14.85 BOP % Interval -19.16 to -10.54	-18.71 BOP % Interval -22.33 to -15.1	-11.00 BOP % Interval -16.83 to -5.17	-10.71 BOP %

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

This biomarker of exposure to a tobacco smoke constituent will be measured in patients who switch to IQOS use and patients who continue cigarette smoking. Concentrations measured in urine and expressed as concentration adjusted for creatinine (mg/g creat).

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Concentrations of Urinary Nicotine Equivalents (NEQ) Baseline	6.777 mg/g creat Interval 5.625 to 8.165	7.649 mg/g creat Interval 6.756 to 8.661	6.452 mg/g creat Interval 3.935 to 10.58	8.527 mg/g creat
Concentrations of Urinary Nicotine Equivalents (NEQ) Month 3	6.766 mg/g creat Interval 5.611 to 8.158	6.699 mg/g creat Interval 5.62 to 7.986	5.911 mg/g creat Interval 3.82 to 9.146	7.681 mg/g creat
Concentrations of Urinary Nicotine Equivalents (NEQ) Month 6	6.471 mg/g creat Interval 5.235 to 7.999	6.563 mg/g creat Interval 5.337 to 8.071	5.467 mg/g creat Interval 3.044 to 9.816	5.213 mg/g creat

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

This biomarker of exposure to a tobacco smoke constituent will be measured in patients who switch to IQOS use and patients who continue cigarette smoking. Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat).

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) Baseline	83.30 pg/mg creat Interval 65.33 to 106.2	112.52 pg/mg creat Interval 92.19 to 137.35	93.01 pg/mg creat Interval 58.11 to 148.84	159.05 pg/mg creat
Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) Mionth 3	25.77 pg/mg creat Interval 20.03 to 33.16	100.67 pg/mg creat Interval 80.95 to 125.2	68.62 pg/mg creat Interval 39.17 to 120.23	124.39 pg/mg creat
Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) Month 6	22.55 pg/mg creat Interval 17.28 to 29.45	96.70 pg/mg creat Interval 75.97 to 123.09	77.17 pg/mg creat Interval 45.8 to 130.03	48.74 pg/mg creat

SECONDARY outcome

Timeframe: From baseline to 3 months and 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment. Subjects were analyzed based on their actual self-reported product use. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

This biomarker of exposure to a tobacco smoke constituent will be measured in patients who switch to IQOS use and patients who continue cigarette smoking. Concentrations measured in urine and expressed as concentration adjusted for creatinine (ng/mg creat).

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Concentrations of 2-cyanoethylmercapturic Acid (CEMA) Baseline	67.29 ng/mg creat Interval 52.25 to 86.67	90.44 ng/mg creat Interval 74.0 to 110.54	92.10 ng/mg creat Interval 59.04 to 143.66	140.95 ng/mg creat
Concentrations of 2-cyanoethylmercapturic Acid (CEMA) Month 3	9.94 ng/mg creat Interval 7.35 to 13.43	80.30 ng/mg creat Interval 63.38 to 101.74	50.36 ng/mg creat Interval 27.16 to 93.41	5.19 ng/mg creat
Concentrations of 2-cyanoethylmercapturic Acid (CEMA) Month 6	7.56 ng/mg creat Interval 5.53 to 10.33	76.65 ng/mg creat Interval 59.37 to 98.97	69.02 ng/mg creat Interval 37.51 to 127.01	1.97 ng/mg creat

SECONDARY outcome

Timeframe: From baseline to 6 months

Population: The analysis population consisted of all randomized subjects with at least one product use experience and at least one valid non-safety assessment analyzed by actual product use. Results were reported only for subjects with exposure to a specific tobacco or nicotine-containing product.

Self-reported use of tobacco or nicotine containing products will be measured over the study in patients switching to IQOS use and patients who continue cigarette smoking.

Outcome measures

Measure	IQOS n=70 Participants IQOS Product Use Category	Cigarette n=84 Participants Cigarette Product Use Category	Dual User n=17 Participants Dual User Product Use Category	Other n=1 Participants Other Product Use Category
Use of Tobacco or Nicotine-containing Products in Patients Switching to IQOS Use and Patients Who Continue Cigarette Smoking. Cigarettes/day over the last five years (Baseline)	18.2 number of product units consumed Interval 16.7 to 19.7	17.7 number of product units consumed Interval 16.6 to 18.9	18.1 number of product units consumed Interval 15.1 to 21.1	20.0 number of product units consumed
Use of Tobacco or Nicotine-containing Products in Patients Switching to IQOS Use and Patients Who Continue Cigarette Smoking. Cigarettes/day	0.22 number of product units consumed Interval 0.1 to 0.34	17.06 number of product units consumed Interval 15.77 to 18.35	8.16 number of product units consumed Interval 3.58 to 12.73	—
Use of Tobacco or Nicotine-containing Products in Patients Switching to IQOS Use and Patients Who Continue Cigarette Smoking. IQOS Heatsticks/day	16.60 number of product units consumed Interval 15.19 to 18.02	0.30 number of product units consumed Interval 0.0 to 3.51	9.06 number of product units consumed Interval 6.86 to 11.25	—
Use of Tobacco or Nicotine-containing Products in Patients Switching to IQOS Use and Patients Who Continue Cigarette Smoking. Other Heat-Not-Burn/day	1.67 number of product units consumed	3.72 number of product units consumed Interval 0.0 to 14.24	0.01 number of product units consumed Interval 0.0 to 0.04	30.00 number of product units consumed
Use of Tobacco or Nicotine-containing Products in Patients Switching to IQOS Use and Patients Who Continue Cigarette Smoking. E-cigarettes/day	2.67 number of product units consumed	—	—	—
Use of Tobacco or Nicotine-containing Products in Patients Switching to IQOS Use and Patients Who Continue Cigarette Smoking. Nicotine Replacement Therapy/day	—	0.81 number of product units consumed	—	0.50 number of product units consumed

Adverse Events

IQOS

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Cigarette

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

Dual

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Other

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	IQOS n=70 participants at risk IQOS users (safety population)	Cigarette n=91 participants at risk Cigarette users (safety population; includes 7 subjects who were enrolled but not randomized and were considered to be in the cigarette users group)	Dual n=17 participants at risk Dual users (safety population)	Other n=1 participants at risk Other users (safety population)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	1.1% 1/91 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/17 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Musculoskeletal and connective tissue disorders Jaw cyst	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	1.1% 1/91 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/17 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.

Other adverse events

Measure	IQOS n=70 participants at risk IQOS users (safety population)	Cigarette n=91 participants at risk Cigarette users (safety population; includes 7 subjects who were enrolled but not randomized and were considered to be in the cigarette users group)	Dual n=17 participants at risk Dual users (safety population)	Other n=1 participants at risk Other users (safety population)
Gastrointestinal disorders Dental caries	8.6% 6/70 • Number of events 6 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	13.2% 12/91 • Number of events 12 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	17.6% 3/17 • Number of events 3 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Gastrointestinal disorders Toothache	5.7% 4/70 • Number of events 4 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	1.1% 1/91 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/17 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Infections and infestations Cellulitis	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/91 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Infections and infestations Oral herpes	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/91 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Infections and infestations Viral upper respiratory tract infection	11.4% 8/70 • Number of events 8 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.5% 5/91 • Number of events 5 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	11.8% 2/17 • Number of events 2 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Injury, poisoning and procedural complications Tooth fracture	2.9% 2/70 • Number of events 2 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	1.1% 1/91 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	100.0% 1/1 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Injury, poisoning and procedural complications Procedural Pain	1.4% 1/70 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	4.4% 4/91 • Number of events 4 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Metabolism and nutrition disorders Gout	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/91 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/91 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/91 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oral papilloma	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/91 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Nervous system disorders Hyperaesthesia	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	2.2% 2/91 • Number of events 2 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	11.8% 2/17 • Number of events 2 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Product Issues Device breakage	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/91 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Product Issues Device failure	1.4% 1/70 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	1.1% 1/91 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/91 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	11.8% 2/17 • Number of events 2 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Gastrointestinal disorders Gingival Pain	2.9% 2/70 • Number of events 2 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	3.3% 3/91 • Number of events 3 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Infections and infestations Gastroenteritis	0.00% 0/70 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/91 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.
Infections and infestations Gingivitis	1.4% 1/70 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/91 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	5.9% 1/17 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.	0.00% 0/1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 31 weeks for each subject. The safety population comprised the 179 subjects enrolled in the study, of which 172 subjects were randomized to the IQOS or Cigarette arms. Adverse events are reported according to subjects' product exposure over the study period (Product Use Category, i.e., IQOS use; Cigarette use; Dual use; or Other use) as detailed in the "Arm/Group" (Reporting Groups) table. The seven subjects who were enrolled but not randomized are included in the Cigarette group for adverse event reporting.

Additional Information

Christelle Haziza, Director Clinical Science & Biostatistics

Philip Morris Products S.A.

Phone: +41 58 242 11 11

Email: ClinicalTrials.PMI@pmi.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER