Biomarkers of exposure (BoE) can help evaluate exposure to combustion-related, tobacco-specific toxicants after smokers switch from cigarettes to potentially less-harmful products like electronic nicotine delivery systems (ENDS). This paper reports data for one (Vuse Solo Original) of three products evaluated in a randomized, controlled, confinement study of BoE in smokers switched to ENDS. Subjects smoked their usual brand cigarette ad libitum for two days, then were randomized to one of three ENDS for a 7-day ad libitum use period, or to smoking abstinence. Thirteen BoE were assessed at baseline and Day 5, and percent change in mean values for each BoE was calculated. Biomarkers of potential harm (BoPH) linked to oxidative stress, platelet activation, and inflammation were also assessed. Levels decreased among subjects randomized to Vuse Solo versus Abstinence, respectively, for the following BoE: 42–96% versus 52–97% (non-nicotine constituents); 51% versus 55% (blood carboxyhemoglobin); and 29% versus 96% (nicotine exposure). Significant decreases were observed in three BoPH: leukotriene E4, 11-dehydro-thromboxane B2, and 2,3-dinor thromboxane B2 on Day 7 in the Vuse Solo and Abstinence groups. These findings show that ENDS use results in substantially reduced exposure to toxicants compared to smoking, which may lead to reduced biological effects.

Electronic nicotine delivery systems (ENDS) have the potential to provide nicotine to tobacco consumers while reducing exposure to combustion-related toxicants. Here, we report changes in biomarkers of exposure (BoE) and biomarkers of potential harm (BoPH) in smokers who completely switched to Vuse Vibe and Vuse Ciro ENDS products, or to smoking abstinence in a randomized, controlled clinical study. Thirteen BoE (12 urinary and one blood) that indicate exposure to harmful and potentially harmful toxicants (HPHCs) were evaluated at baseline on day 5. Urinary BoPH linked to oxidative stress, platelet activation, and inflammation were also assessed at baseline, and on day 5 and day 7. Nicotine exposure was lower in Vuse Vibe and Vuse Ciro groups compared to baseline values. Urinary non-nicotine BoE decreased significantly (52.3–96.7%) in the Vuse ENDS groups, and the reductions were similar in magnitude to those observed in the abstinence group. Blood carboxyhemoglobin decreased 52.8–55.0% in all study groups. Decreases (10–50%) in BoPH were observed in all study groups. Thus, smokers who switch exclusively to Vuse Vibe or Vuse Ciro products or completely abstain from smoking are exposed to substantially lower levels of HPHCs, and experience improvements in BoPH of oxidative stress and inflammation pathways.

Introduction: Oral nicotine pouches (ONPs) are a newer category of smokeless tobacco products containing pharmaceutical-grade nicotine but no tobacco leaf. These products have the potential to help smokers transition away from cigarettes. To assess their potential role as alternatives to cigarettes, we evaluated the abuse liability (AL) of Velo ONPs with varying nicotine content (4–12 mg per pouch), pouch size (600 mg or 400 mg) and flavor (six varieties) in comparison to high (cigarettes) and low (nicotine replacement therapy [NRT] gum) AL comparators.Methods: Independent randomized crossover clinical studies were conducted to assess AL, including subjective effects (product liking [PL], urge to smoke, product effects, overall PL, and overall intent to use again) and nicotine pharmacokinetic (PK) parameters of Velo ONPs. Participants used test products under controlled conditions, and subjective effect measures were collected using validated questionnaires. Nicotine PK parameters, including peak nicotine concentration (C_max), time to maximum concentration (T_max), were assessed.Results: Mean PL scores for all Velo ONPs (p < 0.0042) and Velo Mini Pouches (p < 0.0031) were significantly lower than cigarettes, regardless of nicotine level, pouch size, or flavor, but similar to NRT gum. Other subjective measures for Velo ONPs were less favorable than cigarettes and comparable to or lower than NRT gum. Nicotine uptake with Velo ONPs was slower (reflected by a longer T_max) and had lower C_max than cigarettes but was comparable or slightly lower than NRT gum. Overall nicotine uptake increased with increasing nicotine content and was comparable to that of cigarettes for Velo ONPs with higher nicotine levels. Flavor had no effect on nicotine uptake of Velo ONPs.Discussion: Velo ONPs demonstrated an AL profile lower than cigarettes and similar to NRT gum, suggesting a reduced potential for abuse compared to cigarettes. The slower nicotine uptake and lower peak nicotine levels further support their potential as a lower-risk alternative. These findings highlight the potential role of ONPs in tobacco harm reduction strategies by providing an alternative nicotine source with a lower AL than combustible cigarettes.Systematic Review Registration: The clinical studies were registered at ClinicalTrials.gov; NCT05129657, NCT05294497, and NCT05081154.

Background and Objective Heated tobacco products (HTPs) are a class of non-combustible, inhaled tobacco products with the potential to reduce the harm associated with cigarette smoking due to reduced cigarette smoke toxicant exposure. Subjective and nicotine pharmacokinetics measures taken over the course of product use provide a framework for abuse liability (AL) assessment of tobacco and nicotine products as well as information on adoption potential for a new tobacco product, which are important aspects for premarket tobacco product authorization by the US Food and Drug Administration. This study aimed to assess the AL of glo HTPs, operated in either Standard or Boost Modes, compared with high- and low-AL comparators (subjects’ usual brand cigarettes and nicotine gum, respectively). Methods Nicotine uptake and pharmacodynamics measures (including subjective and physiological measures) were assessed in a clinical study of 75 healthy adult non-menthol or menthol smokers using an open-label, randomized crossover study design. Comparisons were made between glo HTPs (Standard or Boost Modes) and each of usual brand (UB) cigarettes and nicotine gum to evaluate nicotine exposure and subjective effects measures. Results Nicotine uptake, as reflected in the area under the curve (AUC) at 15 and 240 min after product use (AUC_0-15 and AUC_0-240, respectively) and maximum nicotine concentration (C_max) were significantly lower for all glo HTPs compared to UB cigarettes, regardless of the glo device mode. AUC_0-15 values for glo HTPs ranged from 41.26 to 75.71 ng × min/mL, versus 158.04 to 165.53 ng × min/mL for UB cigarettes. Similarly, AUC_0-240 values for glo HTPs ranged from 379 to 596 ng × min/mL, compared to 1123.73 and 1283.37 ng × min/mL for UB cigarettes. The C_max for glo HTPs ranged from 5.46 to 9.00 ng/mL, whereas UB cigarettes had C_max values of 16.29 to 16.76 ng/mL. The time to reach maximum nicotine concentration (T_max) was significantly shorter for glo HTPs (4–5 min) compared to UB cigarettes (6–7 min), except for one variant of glo HTP in Standard Mode. Nicotine gum exhibited a slower nicotine absorption profile, with a T_max of 45 min and C_max of 4.60 ng/mL. AUC_0-15 and AUC_0-240 values for nicotine gum were 6.18 and 5.22 ng × min/mL, and 647.80 and 687.68 ng × min/mL for non-menthol and menthol groups, respectively. Subjective measures indicated that glo HTPs were rated significantly lower than UB cigarettes in terms of product liking, smoking urge reduction, product effects, and intent to use again, but were comparable to nicotine gum. Conclusion glo HTPs demonstrated lower AL than combustible cigarettes while delivering sufficient nicotine to support product adoption among current smokers. This positions glo HTPs as a potential tool in tobacco harm reduction, offering a less harmful alternative to traditional cigarettes. Trial registry Clinical trial ID NCT05114863.

Biomarkers of exposure (BoE) can help evaluate exposure to combustion-related, tobacco-specific toxicants after smokers switch from cigarettes to potentially less-harmful products like electronic nicotine delivery systems (ENDS). This paper reports data for one (Vuse Solo Original) of three products evaluated in a randomized, controlled confinement study of BoE in smokers switched to ENDS. Subjects smoked their usual brand cigarette ad libitum for two days, then were randomized to one of three ENDS for a 7-day ad libitum use period, or to smoking abstinence. Thirteen BoE were assessed at baseline and Day 5, and percent change in mean values for each BoE was calculated. Biomarkers of potential harm (BoPH) linked to oxidative stress, platelet activation, and inflammation were also assessed. Levels decreased among subjects randomized to Vuse Solo versus Abstinence, respectively, for the following BoE: 42–96% vs. 52–97% (non-nicotine constituents); 51% vs. 55% (blood carboxyhemoglobin); and 29% vs. 96% (nicotine exposure). Significant decreases were observed in three BoPH: leukotriene E4, 11-dehydro-thromboxane B2, and 2,3-dinor thromboxane B2 on Day 7 in the Vuse Solo and Abstinence groups. These findings show that ENDS use results in substantially reduced exposure to toxicants compared to smoking, which may lead to reduced biological effects.