Randomized crossover clinical studies to assess abuse liability and nicotine pharmacokinetics of Velo Oral Nicotine pouches

Abstract

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.

Keywords: NRT gum; Velo Oral Nicotine pouches; abuse liability; combustible cigarettes; nicotine uptake; subjective effects; tobacco harm reduction.

FIGURE 1

Summary of overall study design for Velo ONP studies. The Figure includes detailed overview of the timing of nicotine pharmacokinetics (PK) blood draws and completion of subjective effects questionnaires within each 4-h test session. Pharmacokinetics measurements were taken at the indicated timepoints in all three studies, except that Study 3 did not include an 8-min timepoint; product liking (PL), product effects (PE), and urge to smoke (UTS), and overall intent to use again (OIUA) were only administered in Studies 1 and 2; UTS was the only subjective measure administered at baseline in Studies 1 and 2 only; Overall product liking (OPL) was the only subjective measure administered in the Study 3. Both OPL and OIUA were administered at only the 240-min time point. Abbreviations: AL, abuse liability; EOS, end of study; min, minute; UB, usual brand; Velo ONP, Velo oral nicotine pouches.

FIGURE 2

Plasma nicotine concentrations over time for Velo ONPs evaluated in Studies 1 and 2. Each point shows the mean ± SEM plasma nicotine concentration in Study 1 (A) and Study 2 (B). Abbreviations: AL, abuse liability; mg, milligram (of nicotine); ng/mL, nanograms per milliliter; NRT, nicotine replacement therapy; SEM, standard error of the mean; UB, usual brand; Velo ONP, Velo oral nicotine pouches.

FIGURE 3

Urge to smoke scores over 240 min after initiation of product use. Each point shows the mean ± SEM in Study 1 (A) and Study 2 (B). Abbreviations: AL, abuse liability; mg, milligram (of nicotine); NRT, nicotine replacement therapy; SEM, standard error of the mean; UB, usual brand.

FIGURE 4

Plasma nicotine concentrations over 240 min following start of Velo Pouch product use in Study 3. Each point shows the mean ± SEM plasma nicotine concentration. Abbreviations: mg, milligram (of nicotine); PK, pharmacokinetic; SEM, standard error of the mean.