Nicotine Pharmacokinetic and Subjective Assessment of the ...
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Nicotine Pharmacokinetic and Subjective Assessment of the JUUL System with Three Nicotine Concentrations Relative to Combustible Cigarettes in Adult Smokers Nicholas I. Goldenson,1 Ian M. Fearon,2 August R. Buchhalter,3 Jack E. Heningfield3 1Juul Labs, Inc. 2whatIF? Consulting Ltd 3PinneyAssociates, Inc. Introduction • It has been posited that electronic nicotine delivery systems (ENDS) and other alternative nicotine delivery products that more closely mimic the nicotine pharmacokinetics (PK) of cigarettes and relieve cravings for cigarettes and withdrawal symptoms may facilitate smokers transitioning away from cigarettes 1-3 • Previous studies have evaluated the nicotine PK and subjective effects of the JUUL System (JS; Juul Labs, Inc.), a nicotine-salt closed ENDS system, with a 59 mg/mL nicotine concentration 4-6 • Per the European Union’s Revision of the Tobacco Products Directive (EU TPD) the maximum nicotine concentration for ENDS is 20 mg/mL, 7 and there are no existing data evaluating JS with nicotine concentrations below this limit • The primary aim of this study was to assess nicotine PK and subjective effects of JS with three nicotine concentrations: 59 mg/mL, 18 mg/mL and 9 mg/mL compared to combustible cigarettes among adult smokers • A secondary aim was to evaluate if the use of different wicking materials (silica vs. cotton) to draw the e-liquid from the reservoir to the heating coil of the JS affected nicotine PK and subjective effects Methods • Participants (N=24) were adult smokers (mean age [ SD ] = 41.5 [9.93]) • 83% male • All were of white race (not Hispanic or Latino ethnicity) • On average, participants usually smoked 20.3 cigarettes per day (SD=5.57 [Range: 14-29]) and had been smoking for an average of 19.1 years (SD=7.67 [Range: 7-35]) • At each of five study visits, participants used one of four JS products or smoked their UB cigarette during controlled (10 standardized puffs) and then ad libitum (5 minutes) use sessions: 1. JUUL System - 59 mg/mL (Silica Wick) 2. JUUL System - 18 mg/mL (Silica Wick) Results • The time courses of test product plasma nicotine levels over 60 minutes in both the controlled and ad libitum use sessions are displayed in Figure 1 • Maximum plasma nicotine concentration (C max-BL ), total nicotine exposure (AUC 0-60-BL ) and rate of plasma nicotine rise (i.e., speed of nicotine delivery or absorption) were significantly lower for all JS compared to participants’ UB cigarette in both controlled and ad libitum use sessions ( Table 1 ) • In both use sessions C max BL , AUC 0-60-BL and rate of plasma nicotine rise were significantly higher for JS 59 mg/mL compared to JS 18 mg/mL and 9 mg/mL ( Table 1 ) • In the controlled but not the ad libitum use session, significant differences in mean T max between JS 59 mg/mL and 18 mg/mL (cotton wick) and UB cigarettes were observed—this difference in T max is likely due to the cigarette’s significantly higher C max-BL , thus the time it took to reach peak plasma nicotine was longer • For JS 59 mg/mL mean scores on the mPES “Relief” composite subscale (e.g., “Did it immediately relieve your craving for a cigarette?”, “Did it relieve withdrawal symptoms?”) and “Enough Nicotine” subscale item (“Was it enough nicotine?”) did not Conclusions • Nicotine delivery from all JS evaluated was statistically significantly lower than combustible cigarettes • Nicotine exposure and subjective relief from withdrawal and cigarette craving were directly related to the nicotine concentration of the JS: higher nicotine concentrations gave rise to significantly greater plasma nicotine levels and relief from craving • JS 59 mg/mL delivered significantly greater levels of nicotine and significantly reduced craving and withdrawal compared to JS 18 mg/mL and 9 mg/mL • Consistent with having the same nicotine concentration, the two JS 18 mg/mL with different wicking materials (silica vs. cotton) exhibited similar PK profiles and parameters and subjective effects • Use was restricted to a circumscribed period of time (i.e., 10 controlled puffs or 5 minutes of ad libitum use), and it is unknown if PK from JS with different wicking materials would differ over longer periods of use • The lower nicotine delivery and subjective relief from JS 18 mg/mL and 9 mg/mL (vs. 59 mg/mL) may vitiate their ability to act as a satisfying alternative to cigarette smoking • Heavier and more dependent smokers may require the greater nicotine delivery of the JS 59 mg/mL to successfully transition away from cigarettes 1. Administration USFaD. Technical Project Lead Review of IQOS. https://www.fda.gov/media/124247/download. Published 2019. Accessed 26th June, 2020. 2. Abrams DB, Glasser AM, Pearson JL, Villanti AC, Collins LK, Niaura RS. Harm minimization and tobacco control: reframing societal views of nicotine use to rapidly save lives. Annual review of public health. 2018;39:193-213. 3. Gottlieb S, Zeller M. A Nicotine-Focused Framework for Public Health. N Engl J Med. 2017;377(12):1111-1114. 3. JUUL System - 18 mg/mL (Cotton Wick) 4. JUUL System - 9 mg/mL (Cotton Wick) 5. Usual brand (UB) Cigarette • Blood samples were collected 5-minutes prior to the first inhalation (-5) and 1.5-, 3-, 5-, 6-, 7-, 8-, 10-, 15-, 30- and 60-minutes after the first inhalation • The modified Product Evaluation Scale (mPES) assessed subjective effects 30-minutes post-use in the controlled use session • PK parameters and mPES scales were summarised descriptively for each study product; post hoc pairwise comparisons between test products were tested with linear mixed effects models Controlled (CPS) Use Ad Libitum Use Baseline-Adjusted Plasma Nicotine Concentration (ng/mL) Baseline-Adjusted Plasma Nicotine Concentration (ng/mL) 16 14 12 10 8 6 4 2 0 Minutes Relative to Start of Product Use JUUL System 59 mg/mL JUUL System 9 mg/mL End of Test Product Use End of Test Product Use UB Cigarette JUUL System 18 mg/mL (Cotton wick) JUUL System 18 mg/mL (Silica wick) 16 18 14 12 10 8 6 4 2 0 0 10 20 30 40 50 60 PK Parameter JUUL System 59 mg/mL (Silica Wick) JUUL System 18 mg/mL (Silica Wick) JUUL System 18 mg/mL (Cotton Wick) JUUL System 9 mg/mL (Cotton Wick) UB Cigarette Controlled Use Session C max-BL (ng/mL) Mean (SD) 10.6 (5.6) a 3.8 (2.3) b 3.7 (1.7) b 2.4 (1.2) c 17.6 (8.7) d Geometric Mean (SD) 9.3 (1.7) 3.2 (1.8) 3.3 (1.6) 2.1 (1.6) 15.7 (1.6) Median 10.0 3.0 3.5 2.0 14.8 AUC 0-60-BL (hrs × ng/mL) Mean (SD) 5.2 (1.5) a 1.8 (0.6) b 2.0 (0.7) b 1.2 (0.3) c 8.9 (2.7) d Geometric Mean (SD) 5.0 (1.4) 1.7 (1.6) 1.8 (1.4) 1.2 (1.3) 8.5 (1.4) Median 5.1 1.8 1.9 1.2 9.1 Rate of Plasma Nicotine Rise (ng/mL per Minute) Mean (SD) 2.05 (1.45) a 0.71 (0.53) b 0.81 (0.69) b 0.55 (0.51) b 2.80 (1.92) c Median 1.68 0.51 0.58 0.33 2.03 T max (mins) Mean (SD) 6.2 (2.4) a 6.3 (1.6) ab 5.8 (1.8) a 6.6 (5.4) ab 7.8 (5.0) b Median 6.0 6.0 6.0 5.6 7.0 Ad Libitum Use Session C max-BL (ng/mL) Mean (SD) 8.8 (3.2) a 3.8 (1.8) b 3.7 (1.6) b 2.5 (1.0) c 20.9 (11.3) d Geometric Mean (SD) 8.3 (1.4) 3.5 (1.5) 3.3 (1.7) 2.3 (1.6) 18.4 (1.7) Median 8.0 3.2 3.5 2.4 17.3 AUC 0-60-BL (hrs × ng/mL) Mean (SD) 4.8 (1.5) a 1.9 (0.7) b 2.2 (0.7) b 1.3 (0.4) c 9.7 (3.5) d Geometric Mean (SD) 4.6 (1.4) 1.8 (1.5) 2.1 (1.4) 1.2 (1.4) 9.2 (1.4) Median 4.6 1.9 2.1 1.2 8.5 Rate of Plasma Nicotine Rise (ng/mL per Minute) Mean (SD) 1.61 (0.98) a 0.94 (1.44) b 0.71 (0.64) b 0.44 (0.28) b 3.33 (2.03) c Median 1.27 0.50 0.54 0.40 2.63 T max (mins) Mean (SD) 6.4 (2.0) a 6.5 (2.2) a 7.1 (3.2) a 6.7 (2.4) a 6.7 (1.7) a Median 6.1 6.1 6.1 6.2 6.0 mPES JUUL System 59 mg/mL (Silica Wick) JUUL System 18 mg/mL (Silica Wick) JUUL System 18 mg/mL (CottonWick) JUUL System 9 mg/mL (Cotton Wick) UB Cigarette Relief Composite Score Mean (SD) 5.2 (1.0) a 4.6 (1.0) b 4.3 (1.1) bc 3.8 (1.3) c 5.6 (1.3) a Median 5.4 4.4 4.5 4.3 6.0 Min to Max 1.8 to 7.0 2.0 to 7.0 1.4 to 6.2 1.0 to 5.6 2.8 to 7.0 Enough Nicotine Individual Item Mean (SD) 5.9 (1.3) a 4.7 (1.5) b 4.7 (1.7) b 4.0 (1.6) c 6.1 (1.4) a Median 6.0 5.0 5.0 4.0 7.0 Min to Max 2.0 to 7.0 1.0 to 7.0 1.0 to 7.0 1.0 to 7.0 1.0 to 7.0 Satisfaction Composite Score Mean (SD) 4.5 (1.3) a 4.9 (1.1) a 4.6 (1.3) a 4.8 (1.1) a 5.5 (1.4) b Median 4.8 4.9 4.5 5.0 5.9 Min to Max 1.0 to 7.0 2.0 to 7.0 1.3 to 6.8 2.3 to 7.0 2.3 to 7.0 Psychological Reward Composite Score Mean (SD) 4.4 (1.1) acd 4.3 (1.0) abcd 3.9 (1.3) b 4.0 (1.2) a 4.6 (1.2) cd Median 4.6 4.3 4.2 4.0 4.6 Min to Max 1.6 to 6.2 1.6 to 5.8 1.2 to 6.0 1.2 to 6.0 2.8 to 7.0 Aversion Composite Score Mean (SD) 2.4 (1.6) a 1.6 (0.7) bc 1.8 (0.7) bc 1.5 (0.6) b 2.1 (1.2) ac Median 1.9 1.3 1.9 1.5 1.8 Min to Max 1.0 to 6.5 1.0 to 3.0 1.0 to 3.3 1.0 to 3.0 1.0 to 5.3 significantly differ from UB cigarettes ( Table 2 ) • JS 18 mg/mL and 9 mg/mL were rated significantly lower than JS 59 mg/mL and UB cigarettes on mPES “Relief” composite subscale and “Enough Nicotine” item ( Table 2 ) 4. Yingst JM, Hrabovsky S, Hobkirk A, Trushin N, Richie JP, Jr., Foulds J. Nicotine Absorption Profile Among Regular Users of a Pod-Based Electronic Nicotine Delivery System. JAMA Netw Open. 2019;2(11):e1915494. 5. Hajek P, Pittaccio K, Pesola F, Myers Smith K, Phillips-Waller A, Przulj D. Nicotine delivery and users' reactions to Juul compared with cigarettes and other e-cigarette products. Addiction. 2020;115(6):1141-1148. 6. Maloney S, Eversole A, Crabtree M, Soule E, Eissenberg T, Breland A. Acute effects of JUUL and IQOS in cigarette smokers. Tob Control. 2020. doi: 10.1136/tobaccocontrol-2019-055475 7. European Union. Directive 2014/40/EU of the European Parliament and of the Council on the approximation of the laws, regulations and administrative provisions of the Member States concerning the manufacture, presentation and sale of tobacco and related products. Official Journal of the European Union. 2014/40;2014:127 Table 1. PK Parameters of Test Products in Controlled and Ad Libitum Use Sessions Figure 1. Mean Baseline Adjusted Nicotine Concentration by Nominal Time in the Controlled and Ad Libitum Use Sessions. Table 2. mPES Composite Subscale and Individual Item Scores in the Controlled Session Note. N=23-24. Test products in the same row that do not share superscripts significantly differ (p<0.05). Post hoc pairwise differences were tested using multi-level linear models. “Was it enough nicotine?” (“Enough Nicotine”) is an item of the “Relief” subscale. All items were answered on seven point response scales from 1 (“not at all”) to 7 (“extremely”). Note. N=23-24. Test product means in the same row that do not share superscripts significantly differ (p<0.05). References NIG is a full-time employee of Juul Labs, Inc., JEH and ARB are full-time employees of PinneyAssociates, Inc. PinneyAssociates provides consulting services on tobacco harm reduction on an exclusive basis to Juul Labs, Inc. This research was funded by Juul Labs, Inc.
Transcript of Nicotine Pharmacokinetic and Subjective Assessment of the ...
Nicotine Pharmacokinetic and Subjective Assessment of the JUUL System withThree Nicotine Concentrations Relative to Combustible Cigarettes in Adult Smokers
Nicholas I. Goldenson,1 Ian M. Fearon,2 August R. Buchhalter,3 Jack E. Hening�eld3 1Juul Labs, Inc. 2whatIF? Consulting Ltd 3PinneyAssociates, Inc.
Introduction• It has been posited that electronic nicotine delivery systems
(ENDS) and other alternative nicotine delivery products that moreclosely mimic the nicotine pharmacokinetics (PK) of cigarettesand relieve cravings for cigarettes and withdrawal symptoms mayfacilitate smokers transitioning away from cigarettes1-3
• Previous studies have evaluated the nicotine PK and subjectiveeffects of the JUUL System (JS; Juul Labs, Inc.), a nicotine-saltclosed ENDS system, with a 59 mg/mL nicotine concentration4-6
• Per the European Union’s Revision of the Tobacco ProductsDirective (EU TPD) the maximum nicotine concentration for ENDSis 20 mg/mL,7 and there are no existing data evaluating JS withnicotine concentrations below this limit
• The primary aim of this study was to assess nicotine PK andsubjective effects of JS with three nicotine concentrations: 59mg/mL, 18 mg/mL and 9 mg/mL compared to combustiblecigarettes among adult smokers
• A secondary aim was to evaluate if the use of different wickingmaterials (silica vs. cotton) to draw the e-liquid from the reservoirto the heating coil of the JS affected nicotine PK and subjectiveeffects
Methods• Participants (N=24) were adult smokers (mean age [SD] = 41.5
[9.93])• 83% male• All were of white race (not Hispanic or Latino ethnicity)• On average, participants usually smoked 20.3 cigarettes per day
(SD=5.57 [Range: 14-29]) and had been smoking for an averageof 19.1 years (SD=7.67 [Range: 7-35])
• At each of five study visits, participants used one of four JSproducts or smoked their UB cigarette during controlled (10standardized puffs) and then ad libitum (5 minutes) use sessions:1. JUUL System - 59 mg/mL (Silica Wick)2. JUUL System - 18 mg/mL (Silica Wick)
Results• The time courses of test product plasma nicotine levels over 60
minutes in both the controlled and ad libitum use sessions aredisplayed in Figure 1
• Maximum plasma nicotine concentration (Cmax-BL), total nicotineexposure (AUC0-60-BL) and rate of plasma nicotine rise (i.e., speed ofnicotine delivery or absorption) were significantly lower for all JS compared to participants’ UB cigarette in both controlled and ad libitum use sessions (Table 1)
• In both use sessions Cmax BL, AUC0-60-BL and rate of plasma nicotinerise were significantly higher for JS 59 mg/mL compared to JS 18 mg/mL and 9 mg/mL (Table 1)
• In the controlled but not the ad libitum use session, significantdifferences in mean Tmax between JS 59 mg/mL and 18 mg/mL (cotton wick) and UB cigarettes were observed—this difference in Tmax is likely due to the cigarette’s significantly higher Cmax-BL, thus the time it took to reach peak plasma nicotine was longer
• For JS 59 mg/mL mean scores on the mPES “Relief” compositesubscale (e.g., “Did it immediately relieve your craving for acigarette?”, “Did it relieve withdrawal symptoms?”) and “Enough Nicotine” subscale item (“Was it enough nicotine?”) did not
Conclusions• Nicotine delivery from all JS evaluated was statistically significantly
lower than combustible cigarettes• Nicotine exposure and subjective relief from withdrawal and
cigarette craving were directly related to the nicotine concentrationof the JS: higher nicotine concentrations gave rise to significantlygreater plasma nicotine levels and relief from craving
• JS 59 mg/mL delivered significantly greater levels of nicotine andsignificantly reduced craving and withdrawal compared to JS 18mg/mL and 9 mg/mL
• Consistent with having the same nicotine concentration, the two JS18 mg/mL with different wicking materials (silica vs. cotton)exhibited similar PK profiles and parameters and subjective effects
• Use was restricted to a circumscribed period of time (i.e., 10controlled puffs or 5 minutes of ad libitum use), and it is unknown ifPK from JS with different wicking materials would differ over longerperiods of use
• The lower nicotine delivery and subjective relief from JS 18 mg/mLand 9 mg/mL (vs. 59 mg/mL) may vitiate their ability to act as asatisfying alternative to cigarette smoking
• Heavier and more dependent smokers may require the greaternicotine delivery of the JS 59 mg/mL to successfully transition awayfrom cigarettes
1. Administration USFaD. Technical Project Lead Review of IQOS.https://www.fda.gov/media/124247/download. Published 2019. Accessed 26th June, 2020.2. Abrams DB, Glasser AM, Pearson JL, Villanti AC, Collins LK, Niaura RS. Harmminimization and tobacco control: reframing societal views of nicotine use to rapidlysave lives. Annual review of public health. 2018;39:193-213.3. Gottlieb S, Zeller M. A Nicotine-Focused Framework for Public Health. N Engl J Med.2017;377(12):1111-1114.
3. JUUL System - 18 mg/mL (Cotton Wick)4. JUUL System - 9 mg/mL (Cotton Wick)5. Usual brand (UB) Cigarette
• Blood samples were collected 5-minutes prior to the firstinhalation (-5) and 1.5-, 3-, 5-, 6-, 7-, 8-, 10-, 15-, 30- and60-minutes after the first inhalation
• The modified Product Evaluation Scale (mPES) assessedsubjective effects 30-minutes post-use in the controlled usesession
• PK parameters and mPES scales were summarised descriptivelyfor each study product; post hoc pairwise comparisons betweentest products were tested with linear mixed effects models
Controlled (CPS) Use
Ad Libitum Use
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JUUL System59 mg/mL
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JUUL System18 mg/mL (Silica wick)
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PK Parameter JUUL System 59 mg/mL
(Silica Wick)
JUUL System 18 mg/mL
(Silica Wick)
JUUL System 18 mg/mL
(Cotton Wick)
JUUL System 9 mg/mL
(Cotton Wick) UB Cigarette
Controlled Use Session Cmax-BL (ng/mL) Mean (SD) 10.6 (5.6)a 3.8 (2.3)b 3.7 (1.7)b 2.4 (1.2)c 17.6 (8.7)d Geometric Mean (SD) 9.3 (1.7) 3.2 (1.8) 3.3 (1.6) 2.1 (1.6) 15.7 (1.6) Median 10.0 3.0 3.5 2.0 14.8
AUC0-60-BL (hrs × ng/mL) Mean (SD) 5.2 (1.5)a 1.8 (0.6)b 2.0 (0.7)b 1.2 (0.3)c 8.9 (2.7)d Geometric Mean (SD) 5.0 (1.4) 1.7 (1.6) 1.8 (1.4) 1.2 (1.3) 8.5 (1.4) Median 5.1 1.8 1.9 1.2 9.1
Rate of Plasma Nicotine Rise (ng/mL per Minute)Mean (SD) 2.05 (1.45)a 0.71 (0.53)b 0.81 (0.69)b 0.55 (0.51)b 2.80 (1.92)c Median 1.68 0.51 0.58 0.33 2.03
Tmax (mins) Mean (SD) 6.2 (2.4)a 6.3 (1.6)ab 5.8 (1.8)a 6.6 (5.4)ab 7.8 (5.0)b Median 6.0 6.0 6.0 5.6 7.0
Ad Libitum Use Session Cmax-BL (ng/mL) Mean (SD) 8.8 (3.2)a 3.8 (1.8)b 3.7 (1.6)b 2.5 (1.0)c 20.9 (11.3)d Geometric Mean (SD) 8.3 (1.4) 3.5 (1.5) 3.3 (1.7) 2.3 (1.6) 18.4 (1.7) Median 8.0 3.2 3.5 2.4 17.3
AUC0-60-BL (hrs × ng/mL) Mean (SD) 4.8 (1.5)a 1.9 (0.7)b 2.2 (0.7)b 1.3 (0.4)c 9.7 (3.5)d Geometric Mean (SD) 4.6 (1.4) 1.8 (1.5) 2.1 (1.4) 1.2 (1.4) 9.2 (1.4) Median 4.6 1.9 2.1 1.2 8.5
Rate of Plasma Nicotine Rise (ng/mL per Minute)Mean (SD) 1.61 (0.98)a 0.94 (1.44)b 0.71 (0.64)b 0.44 (0.28)b 3.33 (2.03)c Median 1.27 0.50 0.54 0.40 2.63
Tmax (mins) Mean (SD) 6.4 (2.0)a 6.5 (2.2)a 7.1 (3.2)a 6.7 (2.4)a 6.7 (1.7)a Median 6.1 6.1 6.1 6.2 6.0
mPES JUUL System
59 mg/mL (Silica Wick)
JUUL System 18 mg/mL
(Silica Wick)
JUUL System 18 mg/mL
(CottonWick)
JUUL System 9 mg/mL
(Cotton Wick)UB Cigarette
Relief Composite ScoreMean (SD) 5.2 (1.0)a 4.6 (1.0) b 4.3 (1.1) bc 3.8 (1.3)c 5.6 (1.3)a
Median 5.4 4.4 4.5 4.3 6.0Min to Max 1.8 to 7.0 2.0 to 7.0 1.4 to 6.2 1.0 to 5.6 2.8 to 7.0
Enough Nicotine Individual ItemMean (SD) 5.9 (1.3) a 4.7 (1.5) b 4.7 (1.7) b 4.0 (1.6)c 6.1 (1.4)a
Median 6.0 5.0 5.0 4.0 7.0Min to Max 2.0 to 7.0 1.0 to 7.0 1.0 to 7.0 1.0 to 7.0 1.0 to 7.0
Satisfaction Composite ScoreMean (SD) 4.5 (1.3) a 4.9 (1.1)a 4.6 (1.3)a 4.8 (1.1)a 5.5 (1.4)b
Median 4.8 4.9 4.5 5.0 5.9Min to Max 1.0 to 7.0 2.0 to 7.0 1.3 to 6.8 2.3 to 7.0 2.3 to 7.0
Psychological Reward Composite ScoreMean (SD) 4.4 (1.1)acd 4.3 (1.0) abcd 3.9 (1.3) b 4.0 (1.2) a 4.6 (1.2) cd
Median 4.6 4.3 4.2 4.0 4.6Min to Max 1.6 to 6.2 1.6 to 5.8 1.2 to 6.0 1.2 to 6.0 2.8 to 7.0
Aversion Composite ScoreMean (SD) 2.4 (1.6) a 1.6 (0.7) bc 1.8 (0.7) bc 1.5 (0.6) b 2.1 (1.2)ac
Median 1.9 1.3 1.9 1.5 1.8Min to Max 1.0 to 6.5 1.0 to 3.0 1.0 to 3.3 1.0 to 3.0 1.0 to 5.3
significantly differ from UB cigarettes (Table 2)
• JS 18 mg/mL and 9 mg/mL were rated significantly lower than JS59 mg/mL and UB cigarettes on mPES “Relief” compositesubscale and “Enough Nicotine” item (Table 2)
4. Yingst JM, Hrabovsky S, Hobkirk A, Trushin N, Richie JP, Jr., Foulds J. NicotineAbsorption Profile Among Regular Users of a Pod-Based Electronic Nicotine DeliverySystem. JAMA Netw Open. 2019;2(11):e1915494.5. Hajek P, Pittaccio K, Pesola F, Myers Smith K, Phillips-Waller A, Przulj D. Nicotinedelivery and users' reactions to Juul compared with cigarettes and other e-cigaretteproducts. Addiction. 2020;115(6):1141-1148.
6. Maloney S, Eversole A, Crabtree M, Soule E, Eissenberg T, Breland A. Acute effectsof JUUL and IQOS in cigarette smokers. Tob Control. 2020. doi:10.1136/tobaccocontrol-2019-0554757. European Union. Directive 2014/40/EU of the European Parliament and of theCouncil on the approximation of the laws, regulations and administrative provisions ofthe Member States concerning the manufacture, presentation and sale of tobacco andrelated products. Official Journal of the European Union. 2014/40;2014:127
Table 1. PK Parameters of Test Products in Controlled and Ad Libitum Use Sessions
Figure 1. Mean Baseline Adjusted Nicotine Concentration by Nominal Time in the Controlled andAd Libitum Use Sessions.
Table 2. mPES Composite Subscale and Individual Item Scores in the Controlled Session
Note. N=23-24. Test products in the same row that do not share superscripts significantly differ (p<0.05). Post hoc pairwise differences were tested using multi-level linear models. “Was it enough nicotine?” (“Enough Nicotine”) is an item of the “Relief” subscale. All items were answered on seven point response scales from 1 (“not at all”) to 7 (“extremely”).
Note. N=23-24. Test product means in the same row that do not share superscripts significantly differ (p<0.05).
Ref
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NIG is a full-time employee of Juul Labs, Inc., JEH and ARB are full-time employees of PinneyAssociates, Inc.PinneyAssociates provides consulting services on tobacco harm reduction on an exclusive basis to Juul Labs, Inc.
This research was funded by Juul Labs, Inc.
