Trial Outcomes & Findings for Effect of Switching From Cigarette Smoking to IQOS on Exercise Capacity (NCT NCT03887117)

NCT ID: NCT03887117

Last Updated: 2021-12-27

Results Overview

To measure VO2max during maximal cycle ergometer exercise (expressed in absolute values \[mL\*min-1\]).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 94 participants
• Primary outcome timeframe: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43).
• Results posted on: 2021-12-27

Participant Flow

94 subjects were enrolled into the study, but 1 subject was not randomized. 26 subjects were randomized to Cigarette arm, 25 subjects were randomized to IQOS-1 arm, 15 subjects to IQOS-2 arm, and 27 subjects to the Smoking Abstinence (SA) arm. Subjects were requested to use the product allocated to their respective study arm, but it was considered acceptable that not all subjects randomized to the IQOS arms or to the cigarette arm exclusively used the randomized product during the study.

Participant milestones

Measure	IQOS-1 IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program. IQOS + Exercise Training Program: Switch to IQOS use + participation in a training program	IQOS-2 IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Cigarette Smoking Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program. Cigarette Smoking + Exercise Training Program: Continue to smoke cigarettes + participation in a training program	Smoking Abstinence Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program. Smoking Abstinence + Exercise Training Program: Switch to smoking abstinence + participation in a training program
Overall Study STARTED	25	15	26	27
Overall Study COMPLETED	25	14	25	25
Overall Study NOT COMPLETED	0	1	1	2

Reasons for withdrawal

Measure	IQOS-1 IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program. IQOS + Exercise Training Program: Switch to IQOS use + participation in a training program	IQOS-2 IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Cigarette Smoking Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program. Cigarette Smoking + Exercise Training Program: Continue to smoke cigarettes + participation in a training program	Smoking Abstinence Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program. Smoking Abstinence + Exercise Training Program: Switch to smoking abstinence + participation in a training program
Overall Study Discontinued prematurely	0	1	1	2

Baseline Characteristics

Effect of Switching From Cigarette Smoking to IQOS on Exercise Capacity

Baseline characteristics by cohort

Measure	IQOS-1 n=24 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program. IQOS + Exercise Training Program: Switch to IQOS use + participation in a training program	IQOS-2 n=14 Participants No Training Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program. No Training: Switch to IQOS use only, without participation in a training program	Cigarette Smoking n=25 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program. Cigarette Smoking + Exercise Training Program: Continue to smoke cigarettes + participation in a training program	Smoking Abstinence n=27 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program. Smoking Abstinence + Exercise Training Program: Switch to smoking abstinence + participation in a training program	Total n=90 Participants Total of all reporting groups
Age, Continuous	38.8 years STANDARD_DEVIATION 12.8 • n=5 Participants	40.5 years STANDARD_DEVIATION 13.4 • n=7 Participants	40.0 years STANDARD_DEVIATION 10.9 • n=5 Participants	40.2 years STANDARD_DEVIATION 10.3 • n=4 Participants	39.8 years STANDARD_DEVIATION 11.5 • n=21 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants	16 Participants n=4 Participants	49 Participants n=21 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants	11 Participants n=4 Participants	41 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	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) 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	24 Participants n=5 Participants	14 Participants n=7 Participants	25 Participants n=5 Participants	27 Participants n=4 Participants	90 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
Height (cm)	171 cm STANDARD_DEVIATION 10.3 • n=5 Participants	171 cm STANDARD_DEVIATION 10.4 • n=7 Participants	171 cm STANDARD_DEVIATION 8.25 • n=5 Participants	171 cm STANDARD_DEVIATION 9.19 • n=4 Participants	171 cm STANDARD_DEVIATION 9.27 • n=21 Participants
Cigarettes smoked/day (last year)	18.8 cigarettes/day STANDARD_DEVIATION 5.51 • n=5 Participants	17.2 cigarettes/day STANDARD_DEVIATION 4.3 • n=7 Participants	18.0 cigarettes/day STANDARD_DEVIATION 4.69 • n=5 Participants	18.9 cigarettes/day STANDARD_DEVIATION 6.66 • n=4 Participants	18.4 cigarettes/day STANDARD_DEVIATION 5.46 • n=21 Participants

PRIMARY outcome

Timeframe: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure VO2max during maximal cycle ergometer exercise (expressed in absolute values [mL*min-1]).

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=1 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 n=1 Participants Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other n=8 Participants Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Maximal Oxygen Uptake (VO2max, Absolute Values) Acute Baseline (V3)	1878 mL/min Interval 1715.0 to 2040.0	2027 mL/min Interval 1799.0 to 2255.0	2197 mL/min Interval 1788.0 to 2605.0	1950 mL/min Interval 1708.0 to 2191.0	2750 mL/min	1620 mL/min	2103 mL/min Interval 1775.0 to 2430.0
Maximal Oxygen Uptake (VO2max, Absolute Values) Acute Effect (V4)	1823 mL/min Interval 1686.0 to 1960.0	2062 mL/min Interval 1823.0 to 2300.0	2156 mL/min Interval 1747.0 to 2565.0	2071 mL/min Interval 1791.0 to 2351.0	2770 mL/min	1770 mL/min	2094 mL/min Interval 1721.0 to 2466.0
Maximal Oxygen Uptake (VO2max, Absolute Values) Training Effect (V43)	1977 mL/min Interval 1807.0 to 2147.0	2178 mL/min Interval 1889.0 to 2468.0	2150 mL/min Interval 1709.0 to 2591.0	2292 mL/min Interval 1984.0 to 2601.0	—	—	2182 mL/min Interval 1628.0 to 2736.0

PRIMARY outcome

Timeframe: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure VO2max during maximal cycle ergometer exercise (expressed in weight-adjusted [mL*kg-1*min-1] values).

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=1 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 n=1 Participants Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other n=8 Participants Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Maximal Oxygen Uptake (VO2max, Weight-adjusted Values) Acute Baseline (V3)	27.3 mL/(kg*min) Interval 24.8 to 29.8	27.4 mL/(kg*min) Interval 24.9 to 29.9	28.9 mL/(kg*min) Interval 24.6 to 33.3	25.1 mL/(kg*min) Interval 22.9 to 27.3	34.7 mL/(kg*min)	24.4 mL/(kg*min)	25.8 mL/(kg*min) Interval 21.8 to 29.8
Maximal Oxygen Uptake (VO2max, Weight-adjusted Values) Acute Effect (V4)	26.6 mL/(kg*min) Interval 24.4 to 28.8	27.9 mL/(kg*min) Interval 25.1 to 30.7	28.2 mL/(kg*min) Interval 24.4 to 32.0	26.7 mL/(kg*min) Interval 24.0 to 29.4	34.5 mL/(kg*min)	27.0 mL/(kg*min)	25.4 mL/(kg*min) Interval 21.3 to 29.5
Maximal Oxygen Uptake (VO2max, Weight-adjusted Values) Training Effect (V43)	27.9 mL/(kg*min) Interval 25.1 to 30.8	28.8 mL/(kg*min) Interval 25.7 to 31.8	27.7 mL/(kg*min) Interval 23.1 to 32.3	29.6 mL/(kg*min) Interval 26.4 to 32.7	—	—	30.9 mL/(kg*min) Interval 27.9 to 34.0

PRIMARY outcome

Timeframe: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure VO2max during maximal cycle ergometer exercise (expressed in fat-free weight adjusted values [mL*kg-1*min-1]).

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=1 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 n=1 Participants Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other n=8 Participants Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Maximal Oxygen Uptake (VO2max, Fat-free Weight Adjusted Values) Acute Baseline (V3)	37.5 mL/(kg*min) Interval 34.4 to 40.5	38.4 mL/(kg*min) Interval 35.3 to 41.6	38.3 mL/(kg*min) Interval 34.0 to 42.6	34.8 mL/(kg*min) Interval 32.7 to 36.9	44.1 mL/(kg*min)	34.3 mL/(kg*min)	34.4 mL/(kg*min) Interval 29.5 to 39.3
Maximal Oxygen Uptake (VO2max, Fat-free Weight Adjusted Values) Acute Effect (V4)	37.0 mL/(kg*min) Interval 33.8 to 40.2	39.8 mL/(kg*min) Interval 35.6 to 44.0	37.6 mL/(kg*min) Interval 34.3 to 41.0	37.0 mL/(kg*min) Interval 34.6 to 39.5	45.3 mL/(kg*min)	40.2 mL/(kg*min)	34.1 mL/(kg*min) Interval 30.1 to 38.1
Maximal Oxygen Uptake (VO2max, Fat-free Weight Adjusted Values) Training Effect (V43)	40.3 mL/(kg*min) Interval 36.4 to 44.2	39.8 mL/(kg*min) Interval 36.5 to 43.1	38.1 mL/(kg*min) Interval 34.4 to 41.8	42.0 mL/(kg*min) Interval 38.7 to 45.2	—	—	44.7 mL/(kg*min) Interval 36.2 to 53.1

PRIMARY outcome

Timeframe: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43)

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure exercise capacity, by measuring time to complete a pre-defined work (determined as 25% more work than the study subject produced during baseline VO2max test) on a cycle ergometer (seconds).

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=1 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 n=1 Participants Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other n=8 Participants Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Exercise Capacity Acute Baseline (V3)	2283 seconds Interval 2033.0 to 2534.0	2366 seconds Interval 2109.0 to 2623.0	2330 seconds Interval 2013.0 to 2648.0	2156 seconds Interval 1975.0 to 2337.0	2110 seconds	2871 seconds	2147 seconds Interval 1722.0 to 2571.0
Exercise Capacity Acute Effect (V4)	2205 seconds Interval 2017.0 to 2394.0	2189 seconds Interval 1949.0 to 2429.0	2170 seconds Interval 1877.0 to 2462.0	2210 seconds Interval 1921.0 to 2498.0	2402 seconds	3006 seconds	2190 seconds Interval 1820.0 to 2561.0
Exercise Capacity Training Effect (V43)	1985 seconds Interval 1728.0 to 2242.0	2123 seconds Interval 1926.0 to 2319.0	2374 seconds Interval 1970.0 to 2777.0	1849 seconds Interval 1623.0 to 2075.0	—	—	1982 seconds Interval 1465.0 to 2498.0

PRIMARY outcome

Timeframe: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks.

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure cumulative work (calories) produced during each 40 minute exercise training session, performed on a stationary bike, over 12 weeks.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=22 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=5 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Exercise Training Intensity: Cumulative Work Baseline (V5)	169 calorie Interval 145.0 to 193.0	222 calorie Interval 196.0 to 249.0	208 calorie Interval 176.0 to 239.0	203 calorie Interval 108.0 to 297.0	—	—	—
Exercise Training Intensity: Cumulative Work V14	203 calorie Interval 175.0 to 231.0	196 calorie Interval 167.0 to 226.0	231 calorie Interval 200.0 to 261.0	195 calorie Interval 135.0 to 255.0	—	—	—
Exercise Training Intensity: Cumulative Work V29	183 calorie Interval 155.0 to 211.0	197 calorie Interval 159.0 to 235.0	223 calorie Interval 196.0 to 249.0	214 calorie Interval 186.0 to 243.0	—	—	—
Exercise Training Intensity: Cumulative Work V41	187 calorie Interval 161.0 to 212.0	199 calorie Interval 169.0 to 230.0	211 calorie Interval 183.0 to 239.0	219 calorie Interval 80.5 to 357.0	—	—	—

PRIMARY outcome

Timeframe: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks.

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure the average work rate (watt) during each 40 minute exercise training session, performed on a stationary bike, over 12 weeks.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=22 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=5 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Exercise Training Intensity: Average Work Rate Baseline (V5)	70.7 Watt Interval 61.1 to 80.3	87.6 Watt Interval 77.2 to 98.0	84.4 Watt Interval 71.1 to 97.8	82.8 Watt Interval 44.9 to 121.0	—	—	—
Exercise Training Intensity: Average Work Rate V14	81.7 Watt Interval 69.8 to 93.7	78.7 Watt Interval 66.9 to 90.6	90.5 Watt Interval 78.3 to 103.0	80.5 Watt Interval 55.4 to 106.0	—	—	—
Exercise Training Intensity: Average Work Rate V29	74.0 Watt Interval 63.1 to 84.8	80.4 Watt Interval 64.7 to 96.2	90.9 Watt Interval 80.3 to 101.0	85.3 Watt Interval 54.5 to 116.0	—	—	—
Exercise Training Intensity: Average Work Rate V41	76.9 Watt Interval 66.3 to 87.5	82.1 Watt Interval 69.4 to 94.8	85.8 Watt Interval 74.0 to 97.5	89.0 Watt Interval 29.2 to 149.0	—	—	—

PRIMARY outcome

Timeframe: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks.

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure the average heart rate (bpm) during each 40 minute exercise training session, performed on a stationary bike, over 12 weeks.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=22 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=5 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Exercise Training Intensity: Average Heart Rate Baseline (V5)	125 beats/minute Interval 119.0 to 131.0	127 beats/minute Interval 122.0 to 132.0	123 beats/minute Interval 117.0 to 128.0	110 beats/minute Interval 77.7 to 142.0	—	—	—
Exercise Training Intensity: Average Heart Rate V14	119 beats/minute Interval 108.0 to 130.0	127 beats/minute Interval 121.0 to 133.0	121 beats/minute Interval 117.0 to 126.0	125 beats/minute Interval 120.0 to 130.0	—	—	—
Exercise Training Intensity: Average Heart Rate V29	124 beats/minute Interval 116.0 to 131.0	124 beats/minute Interval 118.0 to 130.0	121 beats/minute Interval 116.0 to 125.0	123 beats/minute Interval 113.0 to 133.0	—	—	—
Exercise Training Intensity: Average Heart Rate V41	125 beats/minute Interval 119.0 to 130.0	122 beats/minute Interval 115.0 to 130.0	123 beats/minute Interval 118.0 to 128.0	120 beats/minute Interval 98.0 to 141.0	—	—	—

PRIMARY outcome

Timeframe: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks.

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure the time (seconds) spent at 0-50%, 50-60%, 60-70%, 70-80 % and >80% of maximal heart rate during each 40 minute exercise training session, performed on a stationary bike, over 12 weeks.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=22 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=5 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Exercise Training Intensity: Time Spent at Maximal Heart Rate V5 (Baseline): 0-50%	33.7 seconds Interval 1.0 to 66.4	26.1 seconds Interval -7.68 to 59.8	14.2 seconds Interval -2.15 to 30.5	361 seconds Interval -346.0 to 1068.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate V5 (Baseline): 50-60%	29.7 seconds Interval 6.05 to 53.3	42.2 seconds Interval 14.7 to 69.7	38.6 seconds Interval 18.3 to 58.9	162 seconds Interval -154.0 to 479.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate V5 (Baseline): 60-70%	86.1 seconds Interval 43.8 to 128.0	130 seconds Interval 84.2 to 176.0	131 seconds Interval 78.0 to 184.0	301 seconds Interval -242.0 to 843.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate V5 (Baseline): 70-80%	793 seconds Interval 615.0 to 971.0	737 seconds Interval 586.0 to 888.0	743 seconds Interval 564.0 to 923.0	591 seconds Interval 378.0 to 803.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate V5 (Baseline): >80%	1438 seconds Interval 1193.0 to 1683.0	1405 seconds Interval 1218.0 to 1591.0	1415 seconds Interval 1179.0 to 1650.0	944 seconds Interval -372.0 to 2260.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 14: 0-50%	12.4 seconds Interval 0.479 to 24.4	7.24 seconds Interval 2.73 to 11.7	13.5 seconds Interval 4.26 to 22.8	7.0 seconds Interval -15.3 to 29.3	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 14: 50-60%	25.3 seconds Interval 9.05 to 41.6	32.1 seconds Interval 15.0 to 49.3	38.0 seconds Interval 21.9 to 54.1	28.5 seconds Interval -2.07 to 59.1	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 14: 60-70%	145 seconds Interval 22.7 to 267.0	139 seconds Interval 82.5 to 195.0	188 seconds Interval 80.8 to 295.0	77.8 seconds Interval -50.1 to 206.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 14: 70-80%	807 seconds Interval 616.0 to 997.0	783 seconds Interval 606.0 to 960.0	880 seconds Interval 691.0 to 1068.0	888 seconds Interval 430.0 to 1346.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 14: >80%	1370 seconds Interval 1100.0 to 1641.0	1424 seconds Interval 1197.0 to 1650.0	1260 seconds Interval 993.0 to 1527.0	1386 seconds Interval 764.0 to 2007.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 29: 0-50%	83.1 seconds Interval -62.7 to 229.0	17.2 seconds Interval -0.0182 to 34.4	32.2 seconds Interval -2.92 to 67.3	30.0 seconds Interval -99.1 to 159.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 29: 50-60%	25.3 seconds Interval -7.86 to 58.5	32.9 seconds Interval 4.18 to 61.7	43.0 seconds Interval 13.9 to 72.1	54.7 seconds Interval -157.0 to 267.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 29: 60-70%	120 seconds Interval 42.8 to 197.0	236 seconds Interval 96.3 to 375.0	259 seconds Interval 65.8 to 453.0	130 seconds Interval -277.0 to 538.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 29: 70-80%	731 seconds Interval 524.0 to 938.0	887 seconds Interval 690.0 to 1084.0	732 seconds Interval 544.0 to 920.0	855 seconds Interval 107.0 to 1604.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 29: >80%	1411 seconds Interval 1119.0 to 1704.0	1201 seconds Interval 933.0 to 1468.0	1293 seconds Interval 1032.0 to 1554.0	1286 seconds Interval 212.0 to 2360.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 41: 0-50%	11.1 seconds Interval 2.12 to 20.0	22.6 seconds Interval -4.7 to 50.0	6.60 seconds Interval 1.12 to 12.1	1.33 seconds Interval -4.4 to 7.07	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 41: 50-60%	12.3 seconds Interval 4.77 to 19.9	34.0 seconds Interval 3.49 to 64.5	25.5 seconds Interval 11.2 to 39.8	5.33 seconds Interval -17.6 to 28.3	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 41: 60-70%	99.3 seconds Interval 51.0 to 148.0	308 seconds Interval 59.1 to 557.0	171 seconds Interval 84.6 to 257.0	271 seconds Interval -685.0 to 1226.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 41: 70-80%	871 seconds Interval 609.0 to 1133.0	825 seconds Interval 607.0 to 1043.0	877 seconds Interval 621.0 to 1133.0	1032 seconds Interval -86.6 to 2151.0	—	—	—
Exercise Training Intensity: Time Spent at Maximal Heart Rate Visit 41: >80%	1377 seconds Interval 1066.0 to 1689.0	1185 seconds Interval 842.0 to 1528.0	1293 seconds Interval 968.0 to 1617.0	1091 seconds Interval -999.0 to 3181.0	—	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3) and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure Hemoglobin mass (g), measured with the carbon monoxide-rebreathing method.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Hemoglobin Mass Baseline (V3)	861 g Interval 747.0 to 975.0	796 g Interval 701.0 to 891.0	905 g Interval 808.0 to 1003.0	883 g Interval 755.0 to 1012.0	766 g Interval 290.0 to 1241.0	—	—
Hemoglobin Mass Week 12 (V43)	1194 g Interval 1001.0 to 1387.0	1176 g Interval 1005.0 to 1347.0	1224 g Interval 957.0 to 1490.0	1217 g Interval 966.0 to 1468.0	900 g Interval 454.0 to 1345.0	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3) and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure Red blood cell volume (mL), measured with the carbon monoxide-rebreathing method.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Red Blood Cell Volume Baseline (V3)	2541 mL Interval 2207.0 to 2875.0	2353 mL Interval 2076.0 to 2629.0	2681 mL Interval 2388.0 to 2975.0	2605 mL Interval 2231.0 to 2979.0	2269 mL Interval 871.0 to 3667.0	—	—
Red Blood Cell Volume Week 12 (V43)	3523 mL Interval 2959.0 to 4086.0	3478 mL Interval 2988.0 to 3967.0	3618 mL Interval 2838.0 to 4398.0	3605 mL Interval 2900.0 to 4309.0	2623 mL Interval 1357.0 to 3890.0	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3) and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure Plasma volume (mL), measured with the carbon monoxide-rebreathing method.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Plasma Volume Baseline (V3)	3429 mL Interval 3044.0 to 3814.0	3156 mL Interval 2811.0 to 3500.0	3558 mL Interval 3242.0 to 3874.0	3521 mL Interval 3075.0 to 3966.0	3252 mL Interval 1558.0 to 4946.0	—	—
Plasma Volume Week 12 (V43)	4840 mL Interval 4139.0 to 5542.0	4938 mL Interval 4306.0 to 5570.0	4959 mL Interval 4190.0 to 5729.0	5281 mL Interval 4317.0 to 6245.0	4272 mL Interval 2238.0 to 6307.0	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3) and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure total blood volume (mL), measured with the carbon monoxide-rebreathing method.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Total Blood Volume Baseline (V3)	5970 mL Interval 5282.0 to 6657.0	5508 mL Interval 4914.0 to 6102.0	6239 mL Interval 5709.0 to 6770.0	6126 mL Interval 5326.0 to 6925.0	5521 mL Interval 2443.0 to 8599.0	—	—
Total Blood Volume Week 12 (V43)	8363 mL Interval 7151.0 to 9575.0	8416 mL Interval 7334.0 to 9498.0	8577 mL Interval 7060.0 to 10095.0	8886 mL Interval 7263.0 to 10508.0	6896 mL Interval 3618.0 to 10173.0	—	—

PRIMARY outcome

Timeframe: Measured at Baseline and week 15.

To measure changes from baseline of Capillary blood lactate levels (mmol/L), measured (with a portable lactate analyzer) during VO2max test.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure ventilation (L/min) at VO2max.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=1 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 n=1 Participants Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other n=8 Participants Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Ventilation at VO2 Max Baseline (V3)	74.8 L/min Interval 66.1 to 83.4	78.9 L/min Interval 70.4 to 87.4	87.3 L/min Interval 74.1 to 101.0	71.9 L/min Interval 65.9 to 77.8	109 L/min	55.7 L/min	77.2 L/min Interval 64.8 to 89.6
Ventilation at VO2 Max Acute Effect (V4)	72.0 L/min Interval 66.1 to 77.9	79.1 L/min Interval 70.4 to 87.9	81.3 L/min Interval 67.4 to 95.1	77.2 L/min Interval 69.0 to 85.5	110 L/min	78.6 L/min	76.1 L/min Interval 63.2 to 89.0
Ventilation at VO2 Max Training Effect (V43)	72.7 L/min Interval 64.8 to 80.6	79.2 L/min Interval 69.8 to 88.6	82.5 L/min Interval 67.7 to 97.4	80.3 L/min Interval 73.6 to 87.1	—	—	72.0 L/min Interval 53.8 to 90.3

PRIMARY outcome

Timeframe: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure respiratory rate (breaths per minute) at VO2max.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=1 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 n=1 Participants Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other n=8 Participants Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Respiratory Rate Acute Baseline (V3)	34.5 breaths/minute Interval 31.3 to 37.7	37.5 breaths/minute Interval 33.4 to 41.5	37.1 breaths/minute Interval 30.7 to 43.4	35.2 breaths/minute Interval 32.1 to 38.2	36.0 breaths/minute	29.0 breaths/minute	35.6 breaths/minute Interval 32.3 to 39.0
Respiratory Rate Acute Effect (V4)	34.1 breaths/minute Interval 30.4 to 37.7	37.8 breaths/minute Interval 33.4 to 42.3	35.4 breaths/minute Interval 32.0 to 38.8	36.1 breaths/minute Interval 32.8 to 39.3	38.0 breaths/minute	37.0 breaths/minute	34.1 breaths/minute Interval 30.0 to 38.2
Respiratory Rate Training Effect (V43	33.8 breaths/minute Interval 30.4 to 37.2	37.0 breaths/minute Interval 32.9 to 41.1	33.8 breaths/minute Interval 30.4 to 37.3	36.3 breaths/minute Interval 33.2 to 39.4	—	—	38.4 breaths/minute Interval 29.7 to 47.1

PRIMARY outcome

Timeframe: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure VCO2 (L/min) at VO2 max.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=1 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 n=1 Participants Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other n=8 Participants Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
VCO2 Acute Baseline (V3)	2.21 L/min Interval 2.01 to 2.42	2.36 L/min Interval 2.07 to 2.65	2.58 L/min Interval 2.14 to 3.02	2.24 L/min Interval 2.0 to 2.49	3.23 L/min	1.70 L/min	2.39 L/min Interval 1.98 to 2.8
VCO2 Acute Effect (V4)	2.19 L/min Interval 2.01 to 2.36	2.41 L/min Interval 2.13 to 2.7	2.53 L/min Interval 2.04 to 3.02	2.41 L/min Interval 2.08 to 2.73	3.28 L/min	2.10 L/min	2.38 L/min Interval 1.98 to 2.78
VCO2 Training Effect (V43)	2.36 L/min Interval 2.12 to 2.59	2.53 L/min Interval 2.16 to 2.9	2.53 L/min Interval 2.01 to 3.05	2.67 L/min Interval 2.35 to 2.99	—	—	2.63 L/min Interval 1.96 to 3.29

PRIMARY outcome

Timeframe: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure the respiratory exchange ratio (VCO2/VO2) at VO2max

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=1 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 n=1 Participants Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other n=8 Participants Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Respiratory Exchange Ratio Acute baseline (V3)	1.18 ratio Interval 1.14 to 1.22	1.16 ratio Interval 1.12 to 1.2	1.19 ratio Interval 1.14 to 1.23	1.16 ratio Interval 1.12 to 1.2	1.17 ratio	1.05 ratio	1.14 ratio Interval 1.05 to 1.23
Respiratory Exchange Ratio Acute effect (V4)	1.20 ratio Interval 1.15 to 1.25	1.17 ratio Interval 1.13 to 1.22	1.18 ratio Interval 1.15 to 1.21	1.17 ratio Interval 1.12 to 1.21	1.18 ratio	1.19 ratio	1.14 ratio Interval 1.06 to 1.21
Respiratory Exchange Ratio Training Effect (V43)	1.16 ratio Interval 1.11 to 1.21	1.16 ratio Interval 1.12 to 1.2	1.18 ratio Interval 1.14 to 1.22	1.18 ratio Interval 1.14 to 1.22	—	—	1.21 ratio Interval 1.14 to 1.27

PRIMARY outcome

Timeframe: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure Rating of Perceived Capacity (RPC), determined by using the RPC scale. The RPC scale is a list of physical activities arranged in order, with a scale of values from least strenuous (1) to most exhausting (18 for women, 20 for men). Subjects choose the most strenuous activity, with corresponding value, which they could sustain for 30 minutes.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=1 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 n=1 Participants Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other n=8 Participants Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Rating of Perceived Capacity by Sex Acute Effect - Male (V4)	6.86 Rating of Perceived Capacity Interval 5.73 to 7.98	9.13 Rating of Perceived Capacity Interval 7.68 to 10.6	10.7 Rating of Perceived Capacity Interval 8.53 to 12.9	9.90 Rating of Perceived Capacity Interval 8.53 to 11.3	9.00 Rating of Perceived Capacity	—	6.25 Rating of Perceived Capacity Interval 3.86 to 8.64
Rating of Perceived Capacity by Sex Acute Baseline - Female (V3)	7.77 Rating of Perceived Capacity Interval 5.75 to 9.79	8.22 Rating of Perceived Capacity Interval 6.56 to 9.89	8.17 Rating of Perceived Capacity Interval 5.83 to 10.5	8.00 Rating of Perceived Capacity Interval 7.11 to 8.89	—	5.00 Rating of Perceived Capacity	8.50 Rating of Perceived Capacity Interval 4.5 to 12.5
Rating of Perceived Capacity by Sex Acute Effect - Female (V4)	7.15 Rating of Perceived Capacity Interval 6.46 to 7.84	7.22 Rating of Perceived Capacity Interval 5.31 to 9.14	7.83 Rating of Perceived Capacity Interval 7.4 to 8.26	7.90 Rating of Perceived Capacity Interval 6.34 to 9.46	—	5.00 Rating of Perceived Capacity	8.50 Rating of Perceived Capacity Interval 4.5 to 12.5
Rating of Perceived Capacity by Sex Acute Baseline - Male (V3)	8.00 Rating of Perceived Capacity Interval 6.49 to 9.51	8.25 Rating of Perceived Capacity Interval 7.28 to 9.22	9.71 Rating of Perceived Capacity Interval 7.06 to 12.4	9.70 Rating of Perceived Capacity Interval 7.85 to 11.5	8.00 Rating of Perceived Capacity	—	7.00 Rating of Perceived Capacity Interval 4.09 to 9.91
Rating of Perceived Capacity by Sex Training Baseline - Female (V3)	6.92 Rating of Perceived Capacity Interval 6.04 to 7.79	8.22 Rating of Perceived Capacity Interval 6.56 to 9.89	7.67 Rating of Perceived Capacity Interval 4.96 to 10.4	8.00 Rating of Perceived Capacity Interval 7.21 to 8.79	—	—	10.4 Rating of Perceived Capacity Interval 4.47 to 16.3
Rating of Perceived Capacity by Sex Training Effect - Female (V43)	8.58 Rating of Perceived Capacity Interval 7.27 to 9.9	9.11 Rating of Perceived Capacity Interval 7.55 to 10.7	8.60 Rating of Perceived Capacity Interval 6.18 to 11.0	8.91 Rating of Perceived Capacity Interval 7.49 to 10.3	—	—	9.60 Rating of Perceived Capacity Interval 5.81 to 13.4
Rating of Perceived Capacity by Sex Training Baseline - Male (V3)	7.67 Rating of Perceived Capacity Interval 6.34 to 9.0	8.30 Rating of Perceived Capacity Interval 7.54 to 9.06	9.71 Rating of Perceived Capacity Interval 7.06 to 12.4	9.36 Rating of Perceived Capacity Interval 7.55 to 11.2	—	—	—
Rating of Perceived Capacity by Sex Training Effect - Male (V43)	8.33 Rating of Perceived Capacity Interval 6.26 to 10.4	10.1 Rating of Perceived Capacity Interval 8.69 to 11.5	9.14 Rating of Perceived Capacity Interval 7.34 to 10.9	11.8 Rating of Perceived Capacity Interval 9.24 to 14.4	—	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).

To measure changes from baseline of the Rating of Perceived Exertion, determined by using the Borg scale. The Borg RPE scale is a numerical scale that ranges from 6 to 20, where 6 means "no exertion at all" and 20 means "maximal exertion." Subjects choose a number from the scale that best describes their level of exertion during a physical activity.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Measured at Baseline, at week 1, and at week 15.

To measure changes from baseline of heart rate (bpm) during VO2max test.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Measured at Baseline, at week 1, and at week 15.

To measure changes from baseline of Oxygen uptake during VO2max test. (mL/min)

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure HDL concentrations in serum (mg/dL).

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
High Density Lipoprotein (HDL) Baseline (V3)	49.3 mg/dL Interval 44.9 to 53.7	48.2 mg/dL Interval 40.3 to 56.0	47.1 mg/dL Interval 39.7 to 54.6	52.1 mg/dL Interval 45.6 to 58.7	55.4 mg/dL Interval 48.0 to 62.7	—	—
High Density Lipoprotein (HDL) Week 6 (V14)	48.6 mg/dL Interval 43.8 to 53.4	53.3 mg/dL Interval 45.5 to 61.1	51.0 mg/dL Interval 41.5 to 60.4	53.6 mg/dL Interval 47.4 to 59.7	54.7 mg/dL Interval 47.5 to 61.9	—	—
High Density Lipoprotein (HDL) Week 10 (V28)	51.0 mg/dL Interval 47.5 to 54.4	49.0 mg/dL Interval 41.1 to 57.0	51.8 mg/dL Interval 43.6 to 60.1	53.3 mg/dL Interval 45.9 to 60.7	56.2 mg/dL Interval 47.2 to 65.2	—	—
High Density Lipoprotein (HDL) Week 12 (V43)	47.8 mg/dL Interval 43.2 to 52.4	48.7 mg/dL Interval 41.2 to 56.2	50.1 mg/dL Interval 40.8 to 59.5	55.6 mg/dL Interval 49.6 to 61.7	49.1 mg/dL Interval 44.0 to 54.2	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure LDL concentrations in serum (mg/dL).

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Low Density Lipoprotein (LDL) Baseline (V3)	124 mg/dL Interval 107.0 to 141.0	111 mg/dL Interval 102.0 to 121.0	122 mg/dL Interval 109.0 to 136.0	115 mg/dL Interval 97.9 to 133.0	155 mg/dL Interval 101.0 to 208.0	—	—
Low Density Lipoprotein (LDL) Week 6 (V14)	127 mg/dL Interval 112.0 to 142.0	108 mg/dL Interval 98.8 to 118.0	126 mg/dL Interval 106.0 to 145.0	104 mg/dL Interval 87.3 to 121.0	136 mg/dL Interval 79.4 to 193.0	—	—
Low Density Lipoprotein (LDL) Week 10 (V28)	131 mg/dL Interval 115.0 to 148.0	105 mg/dL Interval 94.4 to 116.0	122 mg/dL Interval 105.0 to 138.0	106 mg/dL Interval 90.0 to 122.0	140 mg/dL Interval 104.0 to 176.0	—	—
Low Density Lipoprotein (LDL) Week 12 (V43)	133 mg/dL Interval 111.0 to 155.0	105 mg/dL Interval 91.6 to 118.0	118 mg/dL Interval 101.0 to 135.0	109 mg/dL Interval 90.5 to 127.0	123 mg/dL Interval 81.5 to 164.0	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure VLDL concentrations in serum (mg/dL).

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Very Low Density Lipoprotein (VLDL) Baseline (V3)	14.7 mg/dL Interval 9.05 to 20.4	13.7 mg/dL Interval 8.29 to 19.1	15.8 mg/dL Interval 10.2 to 21.4	13.7 mg/dL Interval 8.45 to 18.9	12.5 mg/dL Interval -1.89 to 26.9	—	—
Very Low Density Lipoprotein (VLDL) Week 6 (V14)	15.6 mg/dL Interval 5.38 to 25.8	8.30 mg/dL Interval 5.42 to 11.2	11.1 mg/dL Interval 5.63 to 16.6	11.4 mg/dL Interval 6.64 to 16.1	9.82 mg/dL Interval 4.76 to 14.9	—	—
Very Low Density Lipoprotein (VLDL) Week 10 (V28)	14.7 mg/dL Interval 9.06 to 20.4	13.7 mg/dL Interval 0.242 to 27.1	12.0 mg/dL Interval 6.79 to 17.1	6.56 mg/dL Interval 4.86 to 8.25	10.3 mg/dL Interval 5.21 to 15.4	—	—
Very Low Density Lipoprotein (VLDL) Week 12 (V43)	10.7 mg/dL Interval 7.41 to 13.9	12.4 mg/dL Interval 5.34 to 19.5	12.1 mg/dL Interval 6.31 to 18.0	12.3 mg/dL Interval 4.87 to 19.8	10.8 mg/dL Interval 5.91 to 15.6	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure hs-CRP concentrations in serum (mg/dL).

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
High Sensitivity C-reactive Protein (Hs-CRP) Baseline (V3)	2.10 mg/L Interval 0.59 to 3.62	2.19 mg/L Interval 0.983 to 3.4	0.804 mg/L Interval 0.432 to 1.18	1.80 mg/L Interval 0.964 to 2.63	1.17 mg/L Interval -0.754 to 3.09	—	—
High Sensitivity C-reactive Protein (Hs-CRP) Week 6 (V14)	1.40 mg/L Interval 0.805 to 2.0	1.84 mg/L Interval 0.845 to 2.83	1.24 mg/L Interval 0.644 to 1.83	1.43 mg/L Interval 0.833 to 2.03	1.37 mg/L Interval -0.729 to 3.47	—	—
High Sensitivity C-reactive Protein (Hs-CRP) Week 10 (V28)	1.67 mg/L Interval 1.11 to 2.23	2.57 mg/L Interval 1.06 to 4.07	0.815 mg/L Interval 0.438 to 1.19	2.38 mg/L Interval 0.659 to 4.1	1.43 mg/L Interval -0.947 to 3.81	—	—
High Sensitivity C-reactive Protein (Hs-CRP) Week 12 (V43)	1.55 mg/L Interval 0.624 to 2.47	2.79 mg/L Interval 0.399 to 5.19	1.69 mg/L Interval 0.205 to 3.17	1.61 mg/L Interval 0.745 to 2.48	1.26 mg/L Interval -1.08 to 3.6	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure growth hormone concentrations in serum (ng/mL).

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Growth Hormone Baseline (V3)	2.15 ng/mL Interval 0.726 to 3.58	1.37 ng/mL Interval 0.594 to 2.15	2.49 ng/mL Interval 0.059 to 4.93	4.03 ng/mL Interval 0.381 to 7.67	2.02 ng/mL Interval -1.36 to 5.41	—	—
Growth Hormone Week 6 (V14)	1.25 ng/mL Interval 0.452 to 2.06	1.49 ng/mL Interval 0.535 to 2.44	1.22 ng/mL Interval 0.333 to 2.1	1.30 ng/mL Interval 0.444 to 2.16	1.13 ng/mL Interval -1.24 to 3.5	—	—
Growth Hormone Week 10 (V28)	1.45 ng/mL Interval 0.689 to 2.22	0.907 ng/mL Interval 0.394 to 1.42	1.31 ng/mL Interval 0.453 to 2.17	1.97 ng/mL Interval 0.729 to 3.21	0.536 ng/mL Interval 0.0523 to 1.02	—	—
Growth Hormone Week 12 (V43)	1.98 ng/mL Interval 0.487 to 3.47	1.44 ng/mL Interval 0.391 to 2.5	1.94 ng/mL Interval 0.175 to 3.7	1.55 ng/mL Interval 0.582 to 2.51	0.492 ng/mL Interval 0.052 to 0.932	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure glycosylated hemoglobin (HbA1c in whole blood).

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Hemoglobin A1c (HbA1c) Baseline (V3)	5.44 % (of red blood cells) Interval 5.34 to 5.53	5.39 % (of red blood cells) Interval 5.27 to 5.51	5.38 % (of red blood cells) Interval 5.22 to 5.53	5.53 % (of red blood cells) Interval 5.37 to 5.68	5.36 % (of red blood cells) Interval 4.91 to 5.81	—	—
Hemoglobin A1c (HbA1c) Week 6 (V14)	5.41 % (of red blood cells) Interval 5.3 to 5.52	5.35 % (of red blood cells) Interval 5.21 to 5.49	5.41 % (of red blood cells) Interval 5.23 to 5.58	5.50 % (of red blood cells) Interval 5.34 to 5.66	5.28 % (of red blood cells) Interval 4.9 to 5.66	—	—
Hemoglobin A1c (HbA1c) Week 10 (V28)	5.38 % (of red blood cells) Interval 5.27 to 5.49	5.34 % (of red blood cells) Interval 5.22 to 5.46	5.38 % (of red blood cells) Interval 5.18 to 5.57	5.49 % (of red blood cells) Interval 5.32 to 5.65	5.28 % (of red blood cells) Interval 5.0 to 5.56	—	—
Hemoglobin A1c (HbA1c) Week 12 (V43)	5.40 % (of red blood cells) Interval 5.3 to 5.49	5.35 % (of red blood cells) Interval 5.22 to 5.47	5.34 % (of red blood cells) Interval 5.17 to 5.51	5.50 % (of red blood cells) Interval 5.34 to 5.66	5.34 % (of red blood cells) Interval 4.94 to 5.74	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure resting systolic blood pressure in mmHg.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Resting Systolic Blood Pressure Baseline (V3)	118 mmHg Interval 113.0 to 123.0	121 mmHg Interval 116.0 to 127.0	118 mmHg Interval 110.0 to 126.0	122 mmHg Interval 116.0 to 129.0	108 mmHg Interval 101.0 to 114.0	—	—
Resting Systolic Blood Pressure Week 6 (V14)	117 mmHg Interval 113.0 to 122.0	124 mmHg Interval 118.0 to 130.0	120 mmHg Interval 113.0 to 128.0	122 mmHg Interval 116.0 to 128.0	111 mmHg Interval 94.0 to 129.0	—	—
Resting Systolic Blood Pressure Week 10 (V28)	117 mmHg Interval 111.0 to 122.0	121 mmHg Interval 113.0 to 128.0	113 mmHg Interval 107.0 to 119.0	124 mmHg Interval 117.0 to 131.0	110 mmHg Interval 101.0 to 119.0	—	—
Resting Systolic Blood Pressure Week 12 (V43)	116 mmHg Interval 112.0 to 121.0	119 mmHg Interval 112.0 to 126.0	116 mmHg Interval 108.0 to 124.0	122 mmHg Interval 115.0 to 129.0	109 mmHg Interval 101.0 to 117.0	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure resting heart rate in bpm.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Resting Pulse Rate Baseline (V3)	68.8 beats/minute Interval 64.5 to 73.2	68.2 beats/minute Interval 63.8 to 72.5	67.9 beats/minute Interval 61.8 to 74.0	65.8 beats/minute Interval 61.0 to 70.5	73.8 beats/minute Interval 60.3 to 87.3	—	—
Resting Pulse Rate Week 6 (V14)	65.1 beats/minute Interval 62.5 to 67.7	60.0 beats/minute Interval 56.5 to 63.5	63.3 beats/minute Interval 58.9 to 67.7	60.1 beats/minute Interval 56.3 to 63.9	62.2 beats/minute Interval 51.4 to 73.0	—	—
Resting Pulse Rate Week 10 (V28)	65.1 beats/minute Interval 62.1 to 68.2	60.3 beats/minute Interval 56.4 to 64.3	60.7 beats/minute Interval 54.6 to 66.8	59.9 beats/minute Interval 56.0 to 63.8	65.4 beats/minute Interval 50.8 to 80.0	—	—
Resting Pulse Rate Week 12 (V43)	70.5 beats/minute Interval 65.6 to 75.3	65.8 beats/minute Interval 61.4 to 70.2	69.5 beats/minute Interval 63.7 to 75.3	63.9 beats/minute Interval 59.2 to 68.6	73.2 beats/minute Interval 55.2 to 91.2	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure body fat as a percentage.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Body Fat Baseline (V3)	27.8 % (body fat) Interval 24.8 to 30.8	28.2 % (body fat) Interval 24.6 to 31.8	25.6 % (body fat) Interval 20.9 to 30.2	27.3 % (body fat) Interval 23.2 to 31.5	20.5 % (body fat) Interval 14.2 to 26.8	—	—
Body Fat Acute Effect (V4)	28.1 % (body fat) Interval 25.3 to 30.9	28.6 % (body fat) Interval 24.7 to 32.6	25.4 % (body fat) Interval 19.6 to 31.2	28.1 % (body fat) Interval 24.5 to 31.7	28 % (body fat) Interval 20.7 to 35.3	—	—
Body Fat Training Effect (V43)	30.6 % (body fat) Interval 27.5 to 33.7	27.5 % (body fat) Interval 24.3 to 30.8	28 % (body fat) Interval 23.0 to 33.0	29.9 % (body fat) Interval 25.9 to 34.0	30.1 % (body fat) Interval 23.1 to 37.2	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure waist circumference in cm.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Waist Circumference Baseline (V3)	82.6 cm Interval 77.9 to 87.3	83.7 cm Interval 79.0 to 88.5	84.4 cm Interval 80.0 to 88.8	84.9 cm Interval 80.3 to 89.5	78.4 cm Interval 63.5 to 93.3	—	—
Waist Circumference Acute Effect (V4)	82.1 cm Interval 76.6 to 87.5	81.6 cm Interval 76.8 to 86.4	83.6 cm Interval 77.7 to 89.5	85.2 cm Interval 80.4 to 90.1	77.6 cm Interval 63.5 to 91.7	—	—
Waist Circumference Training Effect (V43)	85.8 cm Interval 80.5 to 91.1	86.6 cm Interval 80.2 to 93.1	87.3 cm Interval 78.3 to 96.2	89.5 cm Interval 84.1 to 94.9	86 cm Interval 54.9 to 117.0	—	—

PRIMARY outcome

Timeframe: Measured at each visit, starting from Baseline (V3) until week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure body weight in kilograms.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Body Weight Baseline (V3)	72 kg Interval 66.9 to 77.1	75.7 kg Interval 69.7 to 81.7	75.5 kg Interval 68.7 to 82.3	77.5 kg Interval 72.2 to 82.8	69.3 kg Interval 57.4 to 81.2	—	—
Body Weight Acute Effect (V4)	72.2 kg Interval 67.0 to 77.4	75.7 kg Interval 69.7 to 81.6	75.5 kg Interval 68.5 to 82.4	77.6 kg Interval 72.2 to 83.0	69.6 kg Interval 57.5 to 81.7	—	—
Body Weight Month 1 (V5 - V13)	72 kg Interval 66.9 to 77.0	75.7 kg Interval 69.8 to 81.6	75.7 kg Interval 69.0 to 82.5	77.9 kg Interval 72.4 to 83.3	69.8 kg Interval 57.3 to 82.2	—	—
Body Weight Month 2 (V14 - V27)	72 kg Interval 67.1 to 76.8	75.8 kg Interval 69.7 to 81.9	76.1 kg Interval 69.4 to 82.9	78.1 kg Interval 72.6 to 83.6	70.2 kg Interval 57.2 to 83.1	—	—
Body Weight Month 3 (V28 - V43)	72 kg Interval 67.1 to 76.8	75.8 kg Interval 69.7 to 81.9	76.6 kg Interval 69.6 to 83.5	78.3 kg Interval 72.8 to 83.8	70.5 kg Interval 57.8 to 83.2	—	—

PRIMARY outcome

Timeframe: Measured at each visit, starting from Baseline (V3) until week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure exhaled carbon monoxide (ppm).

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Exhaled Carbon Monoxide Baseline (V3)	20.8 ppm Interval 17.3 to 24.3	20.8 ppm Interval 16.6 to 25.0	19.7 ppm Interval 14.8 to 24.6	18.6 ppm Interval 14.7 to 22.6	20.4 ppm Interval 7.3 to 33.5	—	—
Exhaled Carbon Monoxide Week 1 (V4)	25.4 ppm Interval 20.7 to 30.1	6.16 ppm Interval 2.44 to 9.87	5.46 ppm Interval 2.36 to 8.56	3.55 ppm Interval 2.53 to 4.56	4.80 ppm Interval -0.274 to 9.87	—	—
Exhaled Carbon Monoxide Week 6 (V14)	20.6 ppm Interval 15.3 to 25.9	5.00 ppm Interval 2.84 to 7.16	8.38 ppm Interval -3.78 to 20.6	2.77 ppm Interval 2.32 to 3.23	2.60 ppm Interval 0.717 to 4.48	—	—
Exhaled Carbon Monoxide Week 10 (V28)	20.6 ppm Interval 16.3 to 24.9	4.58 ppm Interval 2.69 to 6.47	4.00 ppm Interval 2.6 to 5.4	2.64 ppm Interval 2.05 to 3.23	2.40 ppm Interval 0.984 to 3.82	—	—
Exhaled Carbon Monoxide Week 12 (V43)	21.8 ppm Interval 16.8 to 26.7	5.79 ppm Interval 2.96 to 8.62	3.17 ppm Interval 1.52 to 4.81	3.05 ppm Interval 2.14 to 3.95	2.00 ppm Interval 0.758 to 3.24	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure Carboxyhemoglobin (COHb), assayed from whole blood. Expressed as % of saturation of hemoglobin.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Carboxyhemoglobin Baseline (V3)	1.92 % (of saturation of hemoglobin) Interval 1.43 to 2.58	2.37 % (of saturation of hemoglobin) Interval 1.82 to 3.09	1.71 % (of saturation of hemoglobin) Interval 1.31 to 2.23	1.74 % (of saturation of hemoglobin) Interval 1.1 to 2.74	2.50 % (of saturation of hemoglobin) Interval 1.1 to 5.69	—	—
Carboxyhemoglobin Week 1 (V4)	3.29 % (of saturation of hemoglobin) Interval 2.61 to 4.16	0.422 % (of saturation of hemoglobin) Interval 0.231 to 0.773	0.372 % (of saturation of hemoglobin) Interval 0.151 to 0.915	0.272 % (of saturation of hemoglobin) Interval 0.163 to 0.456	0.426 % (of saturation of hemoglobin) Interval 0.172 to 1.06	—	—
Carboxyhemoglobin Week 6 (V14)	2.51 % (of saturation of hemoglobin) Interval 1.99 to 3.16	0.350 % (of saturation of hemoglobin) Interval 0.181 to 0.679	0.109 % (of saturation of hemoglobin) Interval 0.0509 to 0.234	0.110 % (of saturation of hemoglobin) Interval 0.0703 to 0.173	0.272 % (of saturation of hemoglobin) Interval 0.0778 to 0.954	—	—
Carboxyhemoglobin Week 10 (V28)	3.01 % (of saturation of hemoglobin) Interval 2.34 to 3.87	0.338 % (of saturation of hemoglobin) Interval 0.19 to 0.601	0.285 % (of saturation of hemoglobin) Interval 0.158 to 0.513	0.189 % (of saturation of hemoglobin) Interval 0.128 to 0.279	0.432 % (of saturation of hemoglobin) Interval 0.052 to 3.58	—	—
Carboxyhemoglobin Week 12 (V43)	2.04 % (of saturation of hemoglobin) Interval 1.6 to 2.61	0.187 % (of saturation of hemoglobin) Interval 0.0868 to 0.402	0.0674 % (of saturation of hemoglobin) Interval 0.0395 to 0.115	0.0864 % (of saturation of hemoglobin) Interval 0.0557 to 0.134	0.132 % (of saturation of hemoglobin) Interval 0.0495 to 0.352	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure Nicotine equivalents (NEQ) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
NEQ Baseline (V3)	14.9 mg/g creat Interval 11.7 to 19.0	14.2 mg/g creat Interval 11.5 to 17.5	10.5 mg/g creat Interval 7.55 to 14.5	12.9 mg/g creat Interval 10.1 to 16.3	14.0 mg/g creat Interval 6.14 to 32.1	—	—
NEQ Week 1 (V4)	13.2 mg/g creat Interval 10.2 to 17.0	10.9 mg/g creat Interval 7.9 to 15.0	7.08 mg/g creat Interval 4.38 to 11.5	4.40 mg/g creat Interval 2.36 to 8.18	8.49 mg/g creat Interval 1.39 to 51.9	—	—
NEQ Week 6 (V14)	13.2 mg/g creat Interval 10.2 to 17.0	10.9 mg/g creat Interval 7.9 to 15.0	7.08 mg/g creat Interval 4.38 to 11.5	4.40 mg/g creat Interval 2.36 to 8.18	9.03 mg/g creat Interval 1.19 to 68.6	—	—
NEQ Week 10 (V28)	14.3 mg/g creat Interval 12.2 to 16.6	11.4 mg/g creat Interval 7.94 to 16.4	8.66 mg/g creat Interval 5.27 to 14.2	1.59 mg/g creat Interval 0.774 to 3.25	11.6 mg/g creat Interval 1.93 to 70.2	—	—
NEQ Week 12 (V43)	13.8 mg/g creat Interval 11.4 to 16.8	12.3 mg/g creat Interval 9.69 to 15.7	5.93 mg/g creat Interval 3.86 to 9.11	2.70 mg/g creat Interval 1.49 to 4.9	5.87 mg/g creat Interval 1.28 to 27.0	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Total NNAL Baseline (V3)	170 pg/mg creat Interval 99.3 to 291.0	239 pg/mg creat Interval 184.0 to 310.0	164 pg/mg creat Interval 87.5 to 307.0	166 pg/mg creat Interval 114.0 to 243.0	244 pg/mg creat Interval 73.3 to 813.0	—	—
Total NNAL Week 1 (V4)	147 pg/mg creat Interval 84.5 to 254.0	88.3 pg/mg creat Interval 45.8 to 170.0	69.9 pg/mg creat Interval 31.9 to 153.0	45.8 pg/mg creat Interval 30.6 to 68.5	97.9 pg/mg creat Interval 38.0 to 252.0	—	—
Total NNAL Week 6 (V14)	177 pg/mg creat Interval 113.0 to 278.0	90.2 pg/mg creat Interval 62.6 to 130.0	62.7 pg/mg creat Interval 31.8 to 123.0	17.4 pg/mg creat Interval 9.53 to 31.9	93.4 pg/mg creat Interval 30.7 to 284.0	—	—
Total NNAL Week 10 (V28)	221 pg/mg creat Interval 155.0 to 315.0	81.3 pg/mg creat Interval 49.3 to 134.0	74.6 pg/mg creat Interval 32.4 to 171.0	26.1 pg/mg creat Interval 12.1 to 56.4	83.3 pg/mg creat Interval 14.1 to 490.0	—	—
Total NNAL Week 12 (V43)	214 pg/mg creat Interval 163.0 to 280.0	82.5 pg/mg creat Interval 46.1 to 148.0	37.9 pg/mg creat Interval 20.7 to 69.4	41.3 pg/mg creat Interval 22.9 to 74.5	62.3 pg/mg creat Interval 21.3 to 182.0	—	—

PRIMARY outcome

Timeframe: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43).

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure 2-cyanoethylmercapturic acid (CEMA) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
CEMA Baseline (V3)	140 ng/mg creat Interval 106.0 to 185.0	170 ng/mg creat Interval 143.0 to 202.0	135 ng/mg creat Interval 97.1 to 188.0	128 ng/mg creat Interval 95.9 to 172.0	144 ng/mg creat Interval 57.3 to 362.0	—	—
CEMA Week 1 (V4)	147 ng/mg creat Interval 114.0 to 189.0	39.5 ng/mg creat Interval 26.8 to 58.4	28.1 ng/mg creat Interval 14.6 to 53.9	25.3 ng/mg creat Interval 18.3 to 34.9	37.5 ng/mg creat Interval 12.9 to 109.0	—	—
CEMA Week 6 (V14)	139 ng/mg creat Interval 104.0 to 185.0	26.6 ng/mg creat Interval 15.8 to 44.8	15.3 ng/mg creat Interval 7.89 to 29.8	12.1 ng/mg creat Interval 8.47 to 17.2	33.1 ng/mg creat Interval 6.1 to 180.0	—	—
CEMA Week 10 (V28)	148 ng/mg creat Interval 113.0 to 194.0	23.6 ng/mg creat Interval 14.4 to 38.7	12.7 ng/mg creat Interval 5.99 to 26.9	11.0 ng/mg creat Interval 7.58 to 15.9	19.3 ng/mg creat Interval 4.88 to 76.0	—	—
CEMA Week 12 (V43)	141 ng/mg creat Interval 108.0 to 183.0	24.8 ng/mg creat Interval 12.4 to 49.4	8.67 ng/mg creat Interval 4.05 to 18.6	12.7 ng/mg creat Interval 7.5 to 21.3	16.5 ng/mg creat Interval 3.9 to 69.7	—	—

PRIMARY outcome

Timeframe: Recorded daily by subject, in product use diary, from study enrollment for 16 weeks.

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure self-reported number of any nicotine/tobacco product used on a daily basis.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Nicotine/Tobacco Product Use (Cigarettes) Pre-randomization (V2-V3)	16.8 cigarettes per day Interval 13.9 to 19.7	19.0 cigarettes per day Interval 16.4 to 21.5	17.4 cigarettes per day Interval 14.3 to 20.4	17.7 cigarettes per day Interval 14.7 to 20.8	24.1 cigarettes per day Interval 18.9 to 29.4	—	—
Nicotine/Tobacco Product Use (Cigarettes) Week 1 (V3-V4)	17.5 cigarettes per day Interval 15.0 to 20.0	0.206 cigarettes per day Interval 0.0 to 0.439	0.242 cigarettes per day Interval 0.0 to 0.556	0.0136 cigarettes per day Interval 0.0 to 0.042	9.72 cigarettes per day Interval 0.0 to 41.4	—	—
Nicotine/Tobacco Product Use (Cigarettes) Up to month 1 (V3-V14)	17.3 cigarettes per day Interval 15.2 to 19.5	0.0351 cigarettes per day Interval 0.0 to 0.0753	0.0623 cigarettes per day Interval 0.0 to 0.132	0.00222 cigarettes per day Interval 0.0 to 0.00683	8.86 cigarettes per day Interval 0.0 to 25.0	—	—
Nicotine/Tobacco Product Use (Cigarettes) Up to month 2 (V3-V26	17.1 cigarettes per day Interval 14.8 to 19.4	0.0196 cigarettes per day Interval 0.0 to 0.0413	0.0369 cigarettes per day Interval 0.0 to 0.0783	0.00132 cigarettes per day Interval 0.0 to 0.00406	8.38 cigarettes per day Interval 0.0 to 24.3	—	—
Nicotine/Tobacco Product Use (Cigarettes) Overall (V3-V43)	17.1 cigarettes per day Interval 14.7 to 19.5	0.0142 cigarettes per day Interval 0.000387 to 0.028	0.0273 cigarettes per day Interval 0.0 to 0.0592	0.000858 cigarettes per day Interval 0.0 to 0.00264	8.34 cigarettes per day Interval 0.0 to 24.3	—	—

PRIMARY outcome

Timeframe: Recorded daily by subject, in product use diary, from study enrollment for 16 weeks.

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure self-reported number of any nicotine/tobacco product used on a daily basis.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Nicotine/Tobacco Product Use (HeatSticks) Overall (V3-V43)	0 heatsticks per day Interval 0.0 to 0.0	19.0 heatsticks per day Interval 14.6 to 23.3	14.1 heatsticks per day Interval 10.9 to 17.2	0 heatsticks per day Interval 0.0 to 0.0	5.08 heatsticks per day Interval 0.0 to 21.3	—	—
Nicotine/Tobacco Product Use (HeatSticks) Pre-randomization (V2-V3)	0 heatsticks per day Interval 0.0 to 0.0	0 heatsticks per day Interval 0.0 to 0.0	0 heatsticks per day Interval 0.0 to 0.0	0 heatsticks per day Interval 0.0 to 0.0	0 heatsticks per day Interval 0.0 to 0.0	—	—
Nicotine/Tobacco Product Use (HeatSticks) Week 1 (V3-V4)	0 heatsticks per day Interval 0.0 to 0.0	17.7 heatsticks per day Interval 13.3 to 22.1	14.1 heatsticks per day Interval 10.5 to 17.7	0 heatsticks per day Interval 0.0 to 0.0	5.81 heatsticks per day Interval 0.0 to 30.8	—	—
Nicotine/Tobacco Product Use (HeatSticks) Up to month 1 (V3-V14)	0 heatsticks per day Interval 0.0 to 0.0	18.6 heatsticks per day Interval 14.4 to 22.9	14.0 heatsticks per day Interval 10.8 to 17.1	0 heatsticks per day Interval 0.0 to 0.0	4.97 heatsticks per day Interval 0.0 to 20.8	—	—
Nicotine/Tobacco Product Use (HeatSticks) Up to month 2 (V3-V26	0 heatsticks per day Interval 0.0 to 0.0	18.7 heatsticks per day Interval 14.5 to 22.9	14.1 heatsticks per day Interval 10.9 to 17.4	0 heatsticks per day Interval 0.0 to 0.0	4.97 heatsticks per day Interval 0.0 to 20.8	—	—

PRIMARY outcome

Timeframe: Recorded daily by subject, in product use diary, from study enrollment for 16 weeks.

Population: AEECS: As Exposed Exercise Compliant Set. Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).

To measure self-reported number of any nicotine/tobacco product used on a daily basis.

Outcome measures

Measure	Cigarette Smoking n=21 Participants Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	IQOS-1 n=19 Participants IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	IQOS-2 n=13 Participants IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=22 Participants Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Dual-1 n=5 Participants Subject randomized to IQOS-1 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Dual-2 Subject randomized to IQOS-2 using ≥30 HeatSticks /month and ≥30 cigarettes/month.	Other Other (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Nicotine/Tobacco Product Use (E-cigarettes) Week 1 (V3-V4)	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	—	—
Nicotine/Tobacco Product Use (E-cigarettes) Up to month 1 (V3-V14)	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	—	—
Nicotine/Tobacco Product Use (E-cigarettes) Up to month 2 (V3-V26	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	—	—
Nicotine/Tobacco Product Use (E-cigarettes) Overall (V3-V43)	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	—	—
Nicotine/Tobacco Product Use (E-cigarettes) Pre-randomization (V2-V3)	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	0.0952 e-cigarettes per day Interval 0.0 to 0.305	0 e-cigarettes per day Interval 0.0 to 0.0	0 e-cigarettes per day Interval 0.0 to 0.0	—	—

Adverse Events

Cigarette Smoking

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

IQOS-1

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

IQOS-2

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Smoking Abstinence

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Other

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cigarette Smoking n=22 participants at risk Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program. Cigarette Smoking + Exercise Training Program: Continue to smoke cigarettes + participation in a training program	IQOS-1 n=22 participants at risk IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program. IQOS + Exercise Training Program: Switch to IQOS use + participation in a training program	IQOS-2 n=13 participants at risk IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=24 participants at risk Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program. Smoking Abstinence + Exercise Training Program: Switch to smoking abstinence + participation in a training program	Other n=12 participants at risk Other product use (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	4.2% 1/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	7.7% 1/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	7.7% 1/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.

Other adverse events

Measure	Cigarette Smoking n=22 participants at risk Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program. Cigarette Smoking + Exercise Training Program: Continue to smoke cigarettes + participation in a training program	IQOS-1 n=22 participants at risk IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program. IQOS + Exercise Training Program: Switch to IQOS use + participation in a training program	IQOS-2 n=13 participants at risk IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Smoking Abstinence n=24 participants at risk Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program. Smoking Abstinence + Exercise Training Program: Switch to smoking abstinence + participation in a training program	Other n=12 participants at risk Other product use (use of \<30 HeatSticks/month and 5-30 cig/month or other forms of product use)
Infections and infestations Nasopharyngitis	36.4% 8/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	13.6% 3/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	23.1% 3/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	12.5% 3/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	25.0% 3/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Infections and infestations Gastroenteritis	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	9.1% 2/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Infections and infestations Gastrointestinal infection	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	7.7% 1/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Musculoskeletal and connective tissue disorders Back pain	13.6% 3/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	9.1% 2/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	4.2% 1/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	8.3% 1/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Musculoskeletal and connective tissue disorders Arthralgia	4.5% 1/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	8.3% 2/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Investigations Blood Tryglycerides Increased	4.5% 1/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	4.5% 1/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	7.7% 1/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	8.3% 2/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Gastrointestinal disorders Gingival bleeding	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	4.5% 1/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Gastrointestinal disorders Nausea	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	9.1% 2/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	8.3% 1/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Gastrointestinal disorders Vomiting	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	4.5% 1/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	8.3% 1/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Gastrointestinal disorders Dental caries	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	7.7% 1/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	9.1% 2/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	15.4% 2/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	4.2% 1/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Respiratory, thoracic and mediastinal disorders Cough	13.6% 3/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	4.5% 1/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	4.2% 1/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	7.7% 1/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	7.7% 1/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Investigations Gamma-glutamyltransferase increased	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	4.2% 1/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	8.3% 1/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Nervous system disorders Headache	4.5% 1/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	7.7% 1/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	16.7% 4/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	8.3% 1/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	8.3% 1/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/22 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/13 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	0.00% 0/24 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.	8.3% 1/12 • 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 24 weeks for each subject. The safety set comprised the 93 subjects enrolled in the study. Adverse events are reported according to the study arm (Cigarette; IQOS-1; IQOS-2; and Smoking Abstinence) that each subject was randomized to.

Additional Information

Christelle Haziza, Global Head Clinical Research and Execution

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