Abuse Liability Assessment of the RELX Infinity^® Electronic Nicotine Delivery System Among Adult Smokers and Electronic Nicotine Delivery System Users

Figure 1.

Figure 2.

Figure 3.

Statistical comparisons of subjective effects measures between Infinity Tobacco and Infinity Menthol and comparator products_ Statistically significant p values are shown in bold text_

	Infinity Tobacco vs comparator			Infinity Menthol vs comparator
	Difference	95% CI (%)	p value	Difference	95% CI (%)	p value
Usual brand cigarette (Study 1)
Urge to smoke Emax_R	13.4 (5.35) a	2.7–24.0	0.0142	11.8 (5.34) a	1.2–22.3	0.0300
Urge to smoke TEmax_R	0.0 (−6.5–5.0) b	−4.00–4.00	1.0000	0.0 (−8.0–12.5) b	−6.00–5.00	0.9920
mPES Satisfaction	−1.6 (0.29) a	−2.2–−1.1	<0.0001	−1.4 (0.29) a	−1.9–−0.8	<0.0001
mPES Psychological reward	−0.9 (0.22) a	−1.4–−0.5	<0.0001	−0.7 (0.22) a	−1.2–−0.3	0.0018
mPES Relief	−1.4 (0.26) a	−1.9–−0.9	<0.0001	−1.3 (0.26) a	−1.9–−0.8	<0.0001
mPES Aversion	0.3 (−0.50–0.63) c	−0.25 – 0.50	0.3075	0.2 (0.119) d	−0.04 – 0.44	0.1045
mPES Concern for dependence	−1.6 (0.30) d	−2.25–−1.02	<0.0001	−1.7 (0.30) d	−2.26–−1.06	<0.0001
Product liking	−23.00 (−58.00–−12.00) c	−49.00–−15.00	<0.0001	−22.00(−61.00–−5.00) c	−33.00–−8.00	<0.0001
Future intent to use	−27.6 (6.66) d	−41.12–−14.15	0.0002	−23.0 (−49.00–−1.00) c	−34.00–−4.00	0.0012
Nicotine gum (Study 1)
Urge to smoke Emax_R	−6.0 (5.39) a	−16.6–4.7	0.2725	−7.6 (5.36) a	−18.2–3.1	0.1611
Urge to smoke TEmax_R	−22.5 (−39.0–−10.0)b	−32.50–−14.00	<0.0001	−17.5 (−34.0–−4.0) b	−28.00–−7.50	0.0006
mPES Satisfaction	0.6 (0.29) a	0.1–1.2	0.0336	0.9 (0.29) a	0.3–1.5	0.0026
mPES Psychological reward	0.6 (0.23) a	0.1–1.0	0.0169	0.8 (0.23) a	0.3–1.2	0.0009
mPES Relief	0.7 (0.27) a	0.2–1.3	0.0070	0.8 (0.27) a	0.3–1.3	0.0040
mPES Aversion	−0.3 (−1.13–0.25) c	−0.75–0.25	0.1516	−0.2 (0.180) d	−0.56–0.17	0.2912
mPES Concern for dependence	1.0 (1.00–3.00) c	−1.00–4.00	0.0923	1.0 (0.00 – 2.00) c	1.00–2.00	0.0768
Product liking	9.08 (5.875) d	−2.843–21.010	0.1311	11.81 (6.603) d	−1.580–25.202	0.0821
Future intent to use	16.9 (8.42) d	−0.17–34.05	0.0522	15.1 (8.86) d	−2.90–33.12	0.0972
Usual brand ENDS (Study 2)
Urge to vape Emax_R	−0.8 (4.22) a	−9.3–7.7	0.8451	2.6 (4.24) a	−5.9–11.1	0.5427
Urge to vape TEmax_R	0.0 (−5.0–15.0) b	−4.00–14.00	0.8434	4.0 (−1.5–13.0) b	−1.50–12.50	0.1706
mPES Satisfaction	−0.8 (0.33) a	−1.4–−0.1	0.0238	0.0 (0.34) a	−0.6–0.7	0.9421
mPES Psychological reward	−0.40 (−1.20–0.40) c	−1.200–0.400	0.3833	0.20 (−0.60–0.80) c	−0.600–0.800	0.8145
mPES Relief	0.01 (0.313) d	−0.636–0.652	0.9806	0.20 (−0.80–1.00) c	−0.400–0.800	0.6776
mPES Aversion	0.05 (0.272) d	−0.512–0.608	0.8610	−0.25 (−0.75–0.63) c	−0.750–0.500	0.8238
mPES Concern for dependence	−0.15 (0.336) d	−0.846–0.538	0.6510	−1.00 (−2.50–2.00) c	−3.000–3.000	0.3877
Product liking Emax	−11.9 (6.85) a	−25.6–1.9	0.0885	1.8 (6.89) a	−12.0–15.6	0.7946
Future intent to use	−13.5 (6.82) d	−27.58–0.50	0.0581	3.0 (−3.00–11.00) c	−3.00–11.00	0.8318

Subject demographics by study_

	Summary statistics / characteristics	Study 1 - Smokers	Study 2 - ENDS Users
N	Number	41	29
Age, years a	Mean (SD)	39.9 (9.51)	39.8 (11.09)
Sex, n (%)	Male	24 (58.5)	17 (58.6)
	Female	17 (41.5)	12 (41.4)
Race, n (%)	White	27 (65.9)	13 (44.8)
	Black or African	13 (31.7)	14 (48.3)
	American
	American Indian or Alaska Native	0 (0)	1 (3.4)
	Other	1 (2.4)	1 (3.4)
Ethnicity, n (%)	Not Hispanic or	39 (95.1)	24 (82.8)
	Latino
	Hispanic or Latino	2 (4.9)	5 (17.2)
Body mass index (kg/m2)	Mean (SD)	29.1 (4.86)	26.6 (4.84)
PS[E]CDI total score b	Mean (SD)	12.1 (2.8)	11.4 (3.6)

Statistical comparison of baseline-adjusted plasma nicotine pharmacokinetic parameters between Infinity Tobacco and Infinity Menthol and comparator products_ Statistically significant p values are shown in bold text_

	Infinity Tobacco vs comparator			Infinity Menthol vs comparator
	Geometric LSmeans Ratio (%)	90% CI (%)	p value	Geometric LSmeans Ratio (%)	90% CI (%)	p value
	Usual brand cigarette (Study 1)
Cmax (ng/mL)	48.3	35.74–65.19	0.0001	45.2	33.36–61.28	< 0.0001
AUC(0–15) (ng×min/mL)	47.4	34.13–65.92	0.0003	44.5	31.99–61.86	< 0.0001
AUC(0–120) (ng×min/mL)	45.5	34.95–59.20	< 0.0001	43.0	33.02–56.03	< 0.0001
Tmax (min)	0.8 (−0.5–2.5)	0.00–1.50	0.0833	0.0 (−1.5–1.0)	−1.00–1.00	0.8504
Nicotine gum (Study 1)
Cmax (ng/mL)	185.6	137.31–250.99	0.0010	173.9	128.31–235.66	0.0032
AUC(0–15) (ng×min/mL)	1426.1	1027.58–1979.30	< 0.0001	1337.5	964.61–1854.61	< 0.0001
AUC(0–120) (ng×min/mL)	107.1	82.05–139.68	0.6715	101.2	77.55–132.16	0.9393
Tmax (min)	−30.0 (−34.0–−26.0)	−33.00–−27.00	< 0.0001	−32.5 (−36.0–−27.0)	−34.00–−28.50	< 0.0001
Usual brand ENDS (Study 2)
Cmax (ng/mL)	109.3	88.71–134.65	0.4784	109.4	88.45–135.20	0.4829
AUC(0–15) (ng×min/mL)	104.7	83.93–130.55	0.7295	107.5	86.08–134.23	0.5874
AUC(0–120) (ng×min/mL)	98.2	83.79–115.05	0.8466	103.2	87.98–121.08	0.7405
Tmax (min)	0.0 (−2.5–3.0)	−2.00–2.50	0.9053	−0.5 (−3.0–5.5)	−2.50–3.00	0.7752

Baseline-adjusted plasma nicotine pharmacokinetic parameters by study and product_

Parameter (units)	Study 1 - Smokers				Study 2 - ENDS Users
	Infinity Tobacco	Infinity Menthol	Usual brand cigarette	Nicotine gum	Infinity Tobacco	Infinity Menthol	Usual brand ENDS
	N	35 a	34	37 b	37 c	27 d	25 e	25 f
Cmax(ng/mL)	18.5 (100.2%)	16.6 (84.9%)	27.0 (60.5%)	7.5 (56.2%)	21.2 (72.5%)	18.2 (51.4%)	16.8 (79.7%)
Tmax(min)	6.0 (2.0, 15.0)	6.0 (2.0, 120.0)	7.0 (2.0, 12.0)	35.0 (15.0,122.0)	8.0 (4.0, 123.0)	8.0 (4.0, 123.0)	8.0 (4.0, 28.0)
AUC(0–15)(ng×min/mL)	171.6 (88.3%)	153.5 (80.2%)	246.00 (50.6%)	12.1 (102.3%)	190.2 (64.4%)	173.5 (51.5%)	160.4 (66.2%)
AUC(0–120)(ng×min/mL)	676.5 (76.2%)	634.1 (76.8%)	1074.8 (31.9%)	530.7 (59.7%)	1046.2 (54.5%)	990.9 (52.0%)	1008.1 (57.2%)

Subjective effects questionnaires by study and product_

	Study 1 - Smokers				Study 2 - ENDS Users
	Infinity Tobacco	Infinity Menthol	Usual brand cigarette	Nicotine gum	Infinity Tobacco	Infinity Menthol	Usual brand ENDS
Urge to smoke/vape [mean (SD)] a
N	38	38 b	38	37	29 c	28 d	25
Emax_R	−49.2 (37.57)	−53.0 (32.29)	−60.5 (31.41)	−48.2 (33.83)	−41.9 (28.32)	−36.8 (29.20)	−43.2 (29.52)
TEmax_R	10.0 (2, 60)	5.0 (2, 120)	10.0 (2, 120)	30.0 (5, 120)	5.0 (2, 60)	10.0 (2, 120)	5.0 (2, 120)
AOE(0–15)	−8.3 (8.57)	−9.3 (6.84)	−10.4 (7.22)	−4.8 (5.58)	−6.1 (5.98)	−5.6 (6.61)	−5.8 (5.76) d
AOE(0–120)	−52.2 (72.28)	−56.5 (49.92)	−69.1 (65.39)	−54.0 (48.46)	−28.1 (49.20)	−38.4 (54.30)	−32.8 (39.34)
Modified product evaluation scale [mean (SD)]
N	39	39	38	36	29	28	26
Satisfaction	3.5 (1.43)	3.8 (1.62)	5.2 (1.63)	2.9 (1.19)	3.8 (1.78)	4.6 (1.58)	4.5 (1.86)
Psychological reward	3.1 (1.38)	3.3 (1.26)	4.1 (1.46)	2.5 (1.10)	3.2 (1.54)	3.7 (1.68)	3.6 (1.76)
Aversion	1.4 (0.46)	1.6 (0.63)	1.4 (0.67)	1.8 (0.96)	1.7 (1.00)	1.7 (1.35)	1.7 (0.85)
Relief	4.2 (1.44)	4.3 (1.45)	5.6 (1.20)	3.5 (1.49)	4.2 (1.48)	4.8 (1.35)	4.2 (1.64)
Concerned for dependence	1.9 (1.48)	1.9 (1.34)	3.6 (2.25)	1.5 (0.81)	2.4 (1.70)	2.3 (2.09)	2.2 (1.58)
Product liking [mean (SD)]
N	38	38	38	37	29	28	25
Emax	56.2 (32.40)	59.6 (35.59)	89.2 (17.15)	47.3 (29.64)	63.8 (32.91)	77.5 (23.95)	74.4 (25.49)
Future intent to use
N	39	39	38	36	29	28	26
Mean (SD)	53.2 (33.26)	51.8 (37.32)	81.7 (24.69)	37.6 (34.15)	55.6 (36.27)	76.5 (28.19)	68.8 (32.99)
Frequency Counts
0–49, n (%)	13 (33.3)	14 (35.9)	4 (10.5)	17 (43.6)	11 (37.9)	5 (17.2)	7 (26.9)
50, n (%)	5 (12.8)	3 (7.7)	0 (0)	2 (5.1)	2 (6.9)	2 (6.9)	1 (3.8)
51–100, n (%)	21 (53.8)	22 (56.4)	34 (89.5)	17 (43.6)	16 (55.2)	21 (72.4)	18 (69.2)