Trial Outcomes & Findings for The Abuse Liability of a Novel Heated Tobacco Product (IQOS) and Its Feasibility as a Menthol Cigarette Substitute (NCT NCT05499377)

Last Updated: 2025-01-31

Results Overview

Average number of cigarettes consumed per day, collected via daily text/email survey, averaged overconsumption for Tues-Thurs of each week. Outcome will compare the percent change in cigarette consumption from the baseline week (OB menthol cigarette use) to the intervention week (IQOS use) between the two study arms.

Recruitment status

COMPLETED

Study phase

Target enrollment

33 participants

Primary outcome timeframe

Week 1 (baseline) to Week 2 (intervention)

Results posted on

2025-01-31

Participant Flow

Participant milestones

Participant milestones
Measure	Tobacco-Flavored IQOS Tobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).	Menthol-Flavored IQOS Menthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).
Overall Study STARTED	15	18
Overall Study COMPLETED	12	18
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Tobacco-Flavored IQOS Tobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).	Menthol-Flavored IQOS Menthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).
Overall Study Withdrawal by Subject	2	0
Overall Study Physician Decision	1	0

Baseline Characteristics

The Abuse Liability of a Novel Heated Tobacco Product (IQOS) and Its Feasibility as a Menthol Cigarette Substitute

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tobacco-Flavored IQOS n=12 Participants Tobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).	Menthol-Flavored IQOS n=18 Participants Menthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	18 Participants n=7 Participants	29 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	46.1 years STANDARD_DEVIATION 12.6 • n=5 Participants	43.0 years STANDARD_DEVIATION 8.3 • n=7 Participants	44.2 years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	13 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	12 Participants n=5 Participants	18 Participants n=7 Participants	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 1 (baseline) to Week 2 (intervention)

Population: Percent change in Average Daily Cigarette Use per day from baseline

Outcome measures

Outcome measures
Measure	Tobacco-Flavored IQOS n=12 Participants Tobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).	Menthol-Flavored IQOS n=18 Participants Menthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).
Percent Change in Average Daily Cigarette Use Per Day From Baseline	36.8 % reduction in cigarettes per day Interval 30.0 to 44.0	80.36 % reduction in cigarettes per day Interval 46.7 to 89.2

PRIMARY outcome

Timeframe: Week 2, Friday Clinical Lab visit

Participants will complete the Experimental Tobacco Marketplace Task - which asks participants to allocate a hypothetical budget across a large menu of products. In each session, cigarette prices increased ($0.12, $0.25, $0.50, $1.00. and $2.00 per cigarette) while prices for alternative products remained fixed. Across three ETM sessions, either all products, all products except little cigars and cigarillos (LCCs), or all products except ENDS (JUUL e-cigarettes) were available. Linear regression is performed on individual participant data using log-transformed cigarette price to determine demand and substitution. Reported demand for tobacco products is used to determine substitution between IQOS and cigarettes. Purchasing decisions are not reinforced. Outcome will compare the cross-price elasticity (CPE) of IQOS with respect to menthol cigarettes among those with access to IQOS-menthol and IQOS-Tobacco (IQOS-M group) compared to those with access to IQOS-tobacco only (IQOS-T group).

Outcome measures

Outcome measures
Measure	Tobacco-Flavored IQOS n=12 Participants Tobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).	Menthol-Flavored IQOS n=18 Participants Menthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).
Percent Increase in Demand as the Subject is Willing to Substitute From Cigarettes to HTPs Using the Experimental Tobacco Marketplace Task	0.14 percent increase in demand/dollars Standard Deviation 0.4	0.67 percent increase in demand/dollars Standard Deviation 0.8

PRIMARY outcome

Timeframe: Week 2, Friday Clinical Lab visit (10 puff bout period)

Change in the plasma nicotine levels from before to after a standardized 10-puff (30-sec interpuff interval) bout with IQOS in the participant's assigned flavor. Outcome will compare the average plasma nicotine boost (the change in plasma nicotine levels from before to after the standardized puffing bout) across two study arms as well as compared to own-brand menthol cigarettes.

Outcome measures

Outcome measures
Measure	Tobacco-Flavored IQOS n=12 Participants Tobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).	Menthol-Flavored IQOS n=18 Participants Menthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).
Plasma Nicotine Delivery	6.3 Nicotine boost (ng/mL) Interval 1.12 to 8.3	6.6 Nicotine boost (ng/mL) Interval 0.4 to 7.7

SECONDARY outcome

Timeframe: Week 2, Friday Clinical Lab Visit (10 puff bout period)

We will compare the degree of "cigarette craving" will be assessed before and after a 10-puff use bout of IQOS. Cigarette craving will be assessed before and after a standardized puffing bout using the Questionnaire of Smoking Urges (QSU), which features 7-point likert-like scales. The reduction in "urges to smoke" item from the QSU will be used in this assessment. The average cigarette craving suppression score will be compared across the two experimental IQOS groups. The Tobacco Craving Questionnaire (TCQ) is a valid and reliable 47-item self-report instrument that assesses tobacco craving in four dimensions: emotionality, expectancy, compulsivity, and purposefulness. The higher your score, the more likely you are to have withdrawal symptoms if you give up smoking; also, the withdrawal symptoms are likely to be stronger

Outcome measures

Outcome measures
Measure	Tobacco-Flavored IQOS n=12 Participants Tobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).	Menthol-Flavored IQOS n=18 Participants Menthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).
Cigarette Craving Suppression Questionnaire	-9.5 change in craving (0-100) scale Interval -45.5 to 2.0	-41.5 change in craving (0-100) scale Interval -62.0 to -16.0

SECONDARY outcome

Timeframe: Week 2, Friday Clinical Lab visit (10 puff bout period)

Average duration per puff during a standardized 10-puff (30-sec interpuff interval) bout with IQOS in assigned flavor. Puff duration will be measured using a validated puff topography instrument that attaches to the IQOS device. Outcome will compare the average puff duration across two study arms.

Outcome measures

Outcome measures
Measure	Tobacco-Flavored IQOS n=12 Participants Tobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).	Menthol-Flavored IQOS n=18 Participants Menthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).
Puff Topography (Puff Duration)	1.64 seconds Interval 1.2 to 2.9	1.33 seconds Interval 1.1 to 2.1

SECONDARY outcome

Timeframe: Week 2 (intervention week), Tuesday-Thursday

Number of IQOS HeatSticks used each day will be assessed during the study. We will compare the number of Heatsticks used per day, on average (from Tues-Thurs of intervention week), between the two study arms.

Outcome measures

Outcome measures
Measure	Tobacco-Flavored IQOS n=12 Participants Tobacco - where menthol smokers will only have access to tobacco-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).	Menthol-Flavored IQOS n=18 Participants Menthol - where menthol smokers will only have access to menthol-flavored HeatSticks to use in the IQOS 2.4 Tobacco Heating System Tobacco product administration and assessment: Participants are first instructed to smoke their usual brand of menthol cigarettes normally for the next 7 days and avoid using any other tobacco products. After this baseline week, participants are randomized to 1 of 2 HTP flavor conditions (tobacco-flavored HeatSticks or Fresh Menthol-flavored HeatSticks), with equal probability and provided with a supply of their condition specific HTP and asked to use it in place of their usual menthol cigarettes for the next week. Participants use their own brand menthol cigarettes and assigned HTP both at home (naturalistic use) and in the clinical laboratory (two visits/week).
Average Daily IQOS Usage	4.5 IQOS sticks per day Interval 1.7 to 6.7	4.3 IQOS sticks per day Interval 3.3 to 9.7

Adverse Events

Tobacco-Flavored IQOS

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Menthol-Flavored IQOS

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Augustus Whiet

Virginia Commonwealth University

Phone: (804) 828-8892

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place