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

Milly Kanobe ^* Christie Powell Patrudu Makena Sarah Baxter Melissa Tapia John Darnell Kristen Prevette Gwyn Gibson Sarah Ayoku Leanne Campbell Jeff Coffield Brian Keyser Bhagya Sukka Nathan Gale Kristen Jordan

• RAI Services Company, Winston-Salem, United States

Oral nicotine pouches (ONPs) are a newer category of smokeless tobacco products that contain pharmaceutical-grade nicotine, but no tobacco leaf. These products have the potential to help smokers transition away from cigarettes. In independent randomized crossover clinical studies, we assessed the abuse liability (AL), including subjective effects and nicotine pharmacokinetic parameters of Velo ONPs with varying nicotine content (4-12 mg per pouch), pouch size (600 mg or 400 mg) and flavor (six varieties), compared to high (cigarettes) and low (nicotine replacement therapy [NRT] gum) AL comparators. Results showed that mean scores for product liking (PL) for all Velo Pouches (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 effects measures (urge to smoke, product effects, overall PL, and overall intent to use again) for Velo ONPs were less favorable than cigarettes and comparable to or lower than NRT gum. Nicotine uptake with use of Velo ONPs was slower (reflected by a longer Tmax) and had lower peak plasma nicotine concentrations (Cmax) relative to cigarettes but was comparable or slightly lower than NRT gum. In Velo ONPs, overall nicotine uptake increased with increasing nicotine content and was comparable to that of cigarettes for the Velo ONPs with higher nicotine levels. Flavor had no effect on nicotine uptake of Velo ONPs. Overall, Velo ONPs demonstrated an AL profile lower than cigarettes and a similar profile to NRT gum, thus, supporting their potential role in tobacco harm reduction strategies.