CHARACTERIZATION OF PUFF TOPOGRAPHY DURING 8- HOURS OF AD LIBITUM USE OF MARKTEN E-VAPOR PRODUCTS Jeffery Edmiston, Qiwei Liang, Andrea Vansickel, Jianmin Liu, Yuxi Zhao, Mohamadi Sarkar Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 1
Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems DRAFT GUIDANCE May 2016 Assessment of user topography (how individual users consume the product, e.g., the number of puffs, puff duration, puff intensity, duration of use), the frequency with which consumers use the product, and the trends by which users consume the product over time; Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 2
Study Objective Characterize the puff topography variables during use of electronic cigarettes by adult conventional cigarette smokers, adult cigarette and e- vapor dual users and adult exclusive e-vapor users. Number of puffs Puff duration Puff volume Puff flow rate Inter-puff interval Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 3
Test Products Unbranded cartridge based e-vapor products E-liquid consisting of: Propylene glycol, glycerol and flavors 2.5% USP grade tobacco-derived nicotine by weight 3.7 volt battery Approximately the size of a King Size traditional cigarette Menthol (M25) and Classic (C25) Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 4
Study Subpopulations: Smokers: Subjects smoked between 10 to 40 cigarettes per day and had not tried e-vapor products Dual Users: Subjects used nicotine containing e-vapor products and conventional cigarettes some days or every day during the past 30 days e-vapor Users: Subjects used nicotine containing e-vapor products for the 6 months before screening and used nicotine containing e-vapor products exclusively some days or every day for the past 30 days Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 5
Study Overview Screening Visit 1 Visit 2 Inclusion/ Exclusion Criteria Test Product trial Subjects had to indicate they definitely, probably or might/might not buy the products after 15 minute trial Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 6
Study Overview Study Day: Visit 3 (8hrs ad libitum use at study site with topography device, fully charged battery and new cartridges provided as needed) Screening Visit 1 Visit 2 Sub- Population Smokers N=30 1hr 1hr 1hr 1hr 1hr 1hr 1hr 1hr A) C25 n=14 B) M25 n=16 Inclusion/ Exclusion Criteria Test Product trial Subjects had to indicate they definitely, probably or might/might not buy the products after 15 minute trial Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 7
Study Overview Study Day: Visit 3 (8hrs ad libitum use at study site with topography device, fully charged battery and new cartridges provided as needed) Inclusion/ Exclusion Criteria Screening Visit 1 Visit 2 Test Product trial Subjects had to indicate they definitely, probably or might/might not buy the products after 15 minute trial Sub- Population Smokers N=30 Dual Users N=30 e-vapor Users N=30 1hr 1hr 1hr 1hr 1hr 1hr 1hr 1hr A) C25 n=14 B) M25 n=16 A) C25 n=13 B) M25 n=17 A) C25 n=14 B) M25 n=16 Start/Restart Topography Recording every hour and after any changing of the e-cigarette Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 8
Puff Topography Measurement Sodim Puff Analyzer / Mobile (SPA/M): Recorded pressure data every 50 milliseconds SODafc v3.30 Analysis: 0.5 second minimum inter-puff interval Software analyzes the first 1600 seconds or the first 50 puffs (whichever occurs first) of each SPA/M recorded file Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 9
Demographics by Study Subpopulation Group Smokers (N=30) Dual Users (N=30) (N=31) Overall (N=91) Age (years) Mean (SD) 34.5 (12.24) 37.6 (10.45) 34.2 (10.73) 35.5 (11.15) Gender (%) Male 15 (50.0%) 14 (46.7%) 19 (61.3%) 48 (52.7%) Female 15 (50.0%) 16 (53.3%) 12 (38.7%) 43 (47.3%) Race (%) Black 9 (30.0%) 10 (33.3%) 3 (9.7%) 22 (24.2%) White 21 (70.0%) 20 (66.7%) 28 (90.3%) 69 (75.8%) Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 10
Tobacco Use History by Subpopulation Ever smoked cigarettes on a consistent basis Current Cigarettes per Day Smokers (N=30) Dual Users (N=30) (N=31) 30 (100%) 30 (100%) 31 (100%) 17.2 (+/-6.4) 13.9 (+/- 6.7) 0 Years smoking 14.6 (+/-10.1) 16.6 (+/-11.44) 16.5 (+/- 10.98) Months vaping 0 12.5 (+/- 7.9) 16.4 (+/- 8.9) Use refillable e-vapor products (+/- SD) 0 15 (50%) 29 (93.5%) Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 11
LS Means (Puff counts) +upper 95%CI Mean Puff Counts by Subpopulation Smokers vs. Dual Users Smokers vs. Dual Users vs. Least Squares (LS) means from ANOVA model LS mean difference (95% CI) -12.68 (-61.80, 36.44) -43.93 (-93.03, 5.16) -31.25 (-80.37, 17.86) Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 12
LS Means (mls) +upper 95%CI Mean Puff Volume by Subpopulation Smokers vs. Dual Users Smokers vs. Dual Users vs. Least Squares (LS) means from ANOVA model LS mean difference (95% CI) -5.59 (-17.15, 5.96) -19.60 (-31.15, -8.04)* -14.00 (-25.56, -2.45)* *Significant difference (95%CI) Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 13
LS Means (sec) +upper 95%CI Mean Puff Duration by Subpopulation Smokers vs. Dual Users Smokers vs. Dual Users vs. Least Squares (LS) means from ANOVA model LS mean difference (95% CI) -0.49 (-1.12, 0.14) -1.82 (-2.45, -1.19)* -1.33 (-1.96, -0.70)* * Significant difference (95% CI) Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 14
LS Means (mls/sec) +upper 95%CI Mean Puff Flow Rate by Subpopulation Smokers vs. Dual Users Smokers vs. Dual Users vs. Least Squares (LS) means from ANOVA model LS mean difference (95% CI) 1.34 (-1.37, 4.05) 5.53 ( 2.82, 8.23)* 4.18 ( 1.47, 6.89)* * Significant difference (95%CI) Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 15
LS Means (sec) +upper 95%CI Inter-Puff Interval by Subpopulation Smokers vs. Dual Users Smokers vs. Dual Users vs. Least Squares (LS) means from ANOVA model LS mean difference (95% CI) 7.49 (-12.80, 27.77) 18.73 ( -1.48, 38.95) 11.25 ( -9.04, 31.53) Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 16
Overall Mean Measurements by Test Product: All Subjects in All Subpopulations Test Product Puff Counts LS Mean (95% CI) Puff Volume (mls) LS Mean (95% CI) Puff Duration (sec) LS Mean (95% CI) Puff Flow Rate (mls/sec) LS Mean (95% CI) Inter-Puff Interval (sec) LS Mean (95% CI) C25 (n=41) 149.21 (119.51, 178.92) 58.18 ( 51.19, 65.17) 3.16 ( 2.77, 3.54) 19.69 (18.05, 21.32) 74.99 ( 62.78, 87.19) M25 (n=49) 134.82 (107.65, 161.99) 59.26 ( 52.87, 65.66) 3.12 ( 2.77, 3.47) 21.18 (19.68, 22.68) 75.93 ( 64.76, 87.09) LS mean difference (95% CI) LS mean difference (95% CI) LS mean difference (95% CI) LS mean difference (95% CI) LS mean difference (95% CI) C25 vs. M25 14.39 (-25.87, 54.66) -1.08 (-10.56, 8.39) 0.04 (-0.48, 0.56) -1.50 (-3.72, 0.73) No significant differences for any comparisons for any parameter, Least Squares (LS) Means from ANOVA model -0.94 (-17.48, 15.60) Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 17
Mean Population Values: All Subjects In All Subpopulations Assessment Mean Puff Counts Mean Puff Volume (mls) Mean Puff Duration (seconds) Mean Puff Flow Rate (mls/sec) Inter-Puff Interval (seconds) Overall (all participants) 141.4 58.77 3.13 20.5 75.24 Standard Deviation +/- 96.12 +/- 23.63 +/- 1.44 +/- 5.75 +/- 39.88 1 st Quartile 85 41.96 2.18 17.49 49.13 3 rd Quartile 172 69.98 3.78 23.68 89.68 Inter-subject % CV Range: 3 subpopulations Intra-subject % CV Range: 3 subpopulations 42-46 28-46 26-39 16-19 60-67 Not applicable 33-44 32-40 12-16 174-182 Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 18
Percent of Puffs Overall Distribution of Puff Volumes: All Puffs Across All Subpopulations 1.1% of measurements were above 210mls Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 19
Percent of Puffs Overall Distribution of Puff Durations: All Puffs Across All Subpopulations 1.2% of measurements were above 10.8 sec Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 20
Percent of Puffs Overall Distribution of Flow Rates: All Puffs Across All Subpopulations Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 21
Summary and Conclusions In general, e-vapor users took longer slower puffs with larger volumes No statistically significant differences in puffing parameters were observed between C25 and M25 e-vapor products The puff topography parameters were highly variable Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 22
Questions? Altria Client Services l RA l CORESTA - ST21 / Oct. 11, 2016 23