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

Karine Renard; Daisuke Nishihara; Johan Nilsson; Sylvain Larroque; Javier Martinez; Lesley Giles

doi:10.1007/s00213-024-06721-7

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

Psychopharmacology (Berl). 2024 Nov 23. doi: 10.1007/s00213-024-06721-7. Online ahead of print.

Authors

Karine Renard^#¹, Daisuke Nishihara^#^{2

3}, Johan Nilsson⁴, Sylvain Larroque², Javier Martinez², Lesley Giles²

Affiliations

¹ JT International (JTI) SA, 8 Rue Kazem Radjavi, 1202, Geneva, Switzerland. karine.renard@jti.com.
² JT International (JTI) SA, 8 Rue Kazem Radjavi, 1202, Geneva, Switzerland.
³ Scientific and Regulatory Affairs, Japan Tobacco Inc, 4-1-1 Toranomon Minato-Ku, Tokyo, 105-6927, Japan.
⁴ CTC Clinical Trial Consultants AB, Dag Hammarskjölds Väg 10B, 752 37, Uppsala, Sweden.

^# Contributed equally.

PMID: 39578274
DOI: 10.1007/s00213-024-06721-7

Abstract

Rationale: 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.

Objectives: To characterize blood nicotine delivery, pharmacokinetics (PK), subjective and physiological effects and to monitor safety of three Nordic Spirit NPs (6 mg, 9 mg and 11.2 mg/pouch) compared with LD tobacco snus (11.2 mg/pouch) and Nicorette® gum (4 mg/unit) following single 30 min use.

Methods: This was a randomized, open-label, ten-sequence, single-use, cross-over clinical study with 30 healthy adult Swedish snus users.

Results: Peak nicotine concentrations (C_max) ranged from 10.92 to 17.32 ng/mL for the three Nordic Spirit NPs, with a trend toward dose proportionality, and 8.18 ng/mL and 9.23 ng/mL for the LD snus and Nicorette® gum comparators, respectively. Peak concentration for Nordic Spirit NPs was reached (T_max) after 30 to 38 min, and after 45 min for LD snus and Nicorette® gum. No notable safety concerns were observed after single use for any of the study products.

Conclusions: Delivery of nicotine from the three Nordic Spirit NPs appeared to be nicotine content-dependent, based on C_max and AUC. The amount of nicotine extracted showed positive correlation with the reported C_max and AUC. For Nordic Spirit NPs, T_max 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.

Keywords: Nicotine; Nicotine pharmacokinetics; Nicotine pouches; Oral nicotine delivery; Safety; Subjective measures; Tobacco-free nicotine pouches.