Characterization of the nicotine uptake and safety of Nordic spirit tobacco-free oral nicotine pouches: A randomized cross-over study.

Abstract

Given the nascency of tobacco-free oral nicotine pouches (NPs) and the heterogeneity of commercially available NP brands, there is a need for scientific evaluation of different NP formulations. Nordic Spirit, novel NPs are distinguished by their unique composition. To characterize blood nicotine delivery, pharmacokinetics (PK), subjective and physiological effects and to monitor safety of three Nordic Spirit NPs (6mg, 9mg and 11.2mg/pouch) compared with LD tobacco snus (11.2mg/pouch) and Nicorette® gum (4mg/unit) following single 30min use. This was a randomized, open-label, ten-sequence, single-use, cross-over clinical study with 30 healthy adult Swedish snus users. Peak nicotine concentrations (Cmax) ranged from 10.92 to 17.32ng/mL for the three Nordic Spirit NPs, with a trend toward dose proportionality, and 8.18ng/mL and 9.23ng/mL for the LD snus and Nicorette® gum comparators, respectively. Peak concentration for Nordic Spirit NPs was reached (Tmax) after 30 to 38min, and after 45min for LD snus and Nicorette® gum. No notable safety concerns were observed after single use for any of the study products. Delivery of nicotine from the three Nordic Spirit NPs appeared to be nicotine content-dependent, based on Cmax and AUC. The amount of nicotine extracted showed positive correlation with the reported Cmax and AUC. For Nordic Spirit NPs, Tmax was immediately after end of use. The characteristics of Nordic Spirit NPs were found to be favourable for profiling NP nicotine delivery and safety in human use, and for further product development. ISRCTN registry study no. ISRCTN75583947.