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Pharmacokinetic Characterization of a Prototype Mini Nicotine Lozenge

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Abstract

Introduction

Cigarette smoking remains a substantial public health problem. Nicotine replacement therapy (NRT) is an effective treatment that increases the success of a quit attempt. There are different NRT formats with no difference in efficacy, but their pharmaceutical form or route of administration may translate into individual preferences. A novel prototype mini lozenge was developed to offer smokers a new NRT option to aid in their quit attempt. Two studies were conducted to characterize the pharmacokinetic parameters and to evaluate its bioequivalence to a commercially available nicotine mini lozenge.

Methods

Two randomized, open-label, crossover studies were conducted to evaluate either the 2 or 4 mg dose level. Heavy smokers in otherwise good health were randomly assigned to one of two treatment sequences: the prototype mini lozenge followed by a commercially available mini lozenge, or the converse. After a 5 to 7 day washout period, subjects crossed over to receive the other study treatment. Blood sampling occurred pre- and post-dose nicotine and was assessed using a validated solid-phase extraction with ultra-high-performance liquid chromatography and tandem mass spectrometry. The primary endpoint was bioequivalence as determined by maximal plasma nicotine concentration (Cmax) and the extent of nicotine absorption (AUC0–t and AUC0–∞). The secondary endpoints included the time to Cmax (Tmax), half-life, the elimination constant (Kel), and safety.

Results

The prototype mini lozenge was bioequivalent to the commercially available mini lozenge, with no significant difference in Cmax, AUC0–t, or AUC0–∞ or any of the secondary outcomes. The most common treatment-emergent adverse event was throat irritation, of which all cases were mild in severity. There were no serious adverse events.

Conclusion

The prototype mini lozenge is bioequivalent to a commercially available mini lozenge and may provide smokers with a new oral NRT option to aid in smoking cessation and of tobacco dependence through the relief of nicotine withdrawal symptoms, including cravings.

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Acknowledgements

We would like to acknowledge and thank the subjects for their participation in these studies.

Funding

Sponsorship for this study and Rapid Service Fee were funded by GlaxoSmithKline.

Authorship

All authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Authorship Contributions

Pamela M Lai contributed to the concept and design of the study and drafting of the manuscript; Mako Araga contributed to the concept and design of the study, the statistical analysis, and the drafting of the manuscript; Ana Hamilton contributed to the concept and design of the study and the drafting of the manuscript; Marianna Armogida contributed to the concept and design of the study and the drafting of the manuscript.

Medical Writing and/or Editorial Assistance

Editorial assistance in the preparation of this article was provided by Andrea S. Blevins Primeau, PhD, MBA, of Medica Communications Inc. Support for this assistance was funded by GlaxoSmithKline.

Disclosures

Pamela M Lai, Mako Araga, Ana Hamilton, and Marianna Armogida are employees of GlaxoSmithKline.

Compliance with Ethics Guidelines

The studies were reviewed and approved by an independent institutional review board: Advarra IRB, 6940 Columbia Gateway Drive, Suite 110, Columbia, Maryland, 21046, USA (IRB# 00000971; IORG # 0000635). The studies were conducted in full compliance of all relevant laws and regulations in the USA and with the requirements specified in the Declaration of Helsinki, and in accordance with the Good Clinical Practice guidelines of the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. All subjects provided written informed consent prior to any study-specific procedures. Subjects could withdraw from either study at any time for any reason.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. GlaxoSmithKline, 184 Liberty Corner Road, Ste 200, Warren, NJ, 07059, USA

    Pamela M. Lai, Mako Araga & Ana Hamilton

  2. GlaxoSmithKline, Route de l’Etraz 2, Case postale, 1260, Nyon 1, Switzerland

    Marianna Armogida

Authors
  1. Pamela M. Lai
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  2. Mako Araga
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  3. Ana Hamilton
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  4. Marianna Armogida
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Corresponding author

Correspondence to Pamela M. Lai.

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Lai, P.M., Araga, M., Hamilton, A. et al. Pharmacokinetic Characterization of a Prototype Mini Nicotine Lozenge. Adv Ther 38, 3997–4012 (2021). https://doi.org/10.1007/s12325-021-01798-4

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  • DOI: https://doi.org/10.1007/s12325-021-01798-4

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