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

Graff, Donald W.; Fearon, Ian M.; McClean, Mark; Melara, Rebeca; Vemuri, Ramadevi; Mills, Catherine

doi:10.2478/cttr-2025-0012

Figures & Tables

Overview of study designs. In both studies, subjects underwent an 8-h ad libitum (AL) use session, after which they abstained from any nicotine product use for 10–13 h prior to nicotine pharmacokinetic (PK) sessions the following day. This sequence was followed once for each study product, in a randomized order. Each product use study period was completed over approximately 24 h. Subjects were confined to the clinic site throughout the assessments.

Mean baseline-adjusted plasma nicotine concentration-time profiles in (a) smokers (Study 1) and (b) ENDS users (Study 2). Error bars have been removed for clarity; for variability estimates refer to Table 2.

Mean urge to smoke/vape VAS scores over time profiles in (a) smokers (Study 1) and (b) ENDS users (Study 2). Error bars have been removed for clarity; for variability estimates refer to Table 4.

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 E_{max_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 TE_{max_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 E_{max_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 TE_{max_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 E_{max_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 TE_{max_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 E_max	−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)
Sex, n (%)	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)
C_max (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
T_max (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)
C_max (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
T_max (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)
C_max (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
T_max (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
C_max(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%)
T_max(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
E_{max_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)
TE_{max_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
E_max	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)

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

Figures & Tables

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_

Subject demographics by study_

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_

Baseline-adjusted plasma nicotine pharmacokinetic parameters by study and product_

Subjective effects questionnaires by study and product_

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