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Pharmacokinetics of Nasal Esketamine in Patients with Allergic Rhinitis with and Without Nasal Decongestant Pretreatment and in Healthy Subjects with and Without Nasal Corticosteroid Pretreatment

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A Correction to this article was published on 05 August 2023

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Abstract

Background and Objectives

Nasal esketamine is indicated for the treatment of adults with treatment-resistant depression and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. Primary objectives of this study were to evaluate the effect of nasal decongestant pretreatment in patients with allergic rhinitis and the impact of daily nasal corticosteroid administration by healthy subjects on nasal esketamine pharmacokinetics.

Methods

Patients with allergic rhinitis self-administered 56 mg of nasal esketamine after pretreatment with nasal oxymetazoline (0.05%) at 1 h before esketamine and without oxymetazoline pretreatment. They were exposed to grass pollen in an allergen challenge chamber to induce allergic rhinitis symptoms at approximately 2 h before each esketamine administration until 1 h after. Healthy subjects self-administered esketamine (56 mg) before and after administration for 16 consecutive days of mometasone (200 µg), with the second esketamine dose administered 1 h after the last mometasone dose. The plasma pharmacokinetics of esketamine and noresketamine were assessed after each esketamine administration. The tolerability of esketamine, including effects on dissociative and potential psychotomimetic symptoms and level of sedation and suicidal ideation and behavior, was evaluated.

Results

The rate of esketamine absorption was slightly greater in patients exhibiting symptoms of allergic rhinitis (decrease in median tmax from 32 min to 22 min). Increases in esketamine Cmax and AUC were also small (mean, ≤ 21%). The pharmacokinetics of esketamine was not affected by oxymetazoline or mometasone pretreatment. Esketamine was well tolerated when it was administered with or without pretreatment of oxymetazoline or mometasone.

Conclusions

Patients exhibiting symptoms of rhinitis may receive nasal esketamine spray without dose adjustment. In addition, esketamine may be administered 1 h after using a nasal decongestant or corticosteroid.

Trial Registration

The study was registered in the Clinical Trials (NCT02154334) and EudraCT (2014‐000534‐38) registries.

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Authors and Affiliations

  1. Janssen R&D, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA

    Peter Zannikos

  2. Janssen R&D, 6050 Paseo Carreta, Carlsbad, CA, 92009, USA

    Bhavna Solanki

  3. Janssen R&D, Turnhoutseweg 30, Beerse, 2340, Antwerp, Belgium

    Marc De Meulder

  4. Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine, Feodor-Lynen-Str. 15, 30625, Hannover, Germany

    Philipp Badorrek

  5. Department of Respiratory Science, Fraunhofer Institute for Toxicology and Experimental Medicine, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Jens M. Hohlfeld

  6. German Center for Lung Research (DZL), BREATH, Hannover, Germany

    Jens M. Hohlfeld

  7. Neurocrine Bioscience, Inc, 12780 El Camino Real, San Diego, CA, 92130, USA

    Jaskaran Singh

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Correspondence to Peter Zannikos.

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Funding

The clinical study and the analyses presented were supported by research funding from Janssen Research and Development, LLC.

Conflict of Interest

Peter Zannikos, Bhavna Solanki, Marc De Meulder, and Jaskaran Singh were employed by Janssen Research & Development, LLC at the time the study was conducted and, as such, may have been eligible for stock and stock options.

Data Availability and Material

The datasets generated and/or analyzed during the study belong to Janssen Research & Development, LLC and are not publicly available.

Ethics Approval

The protocol was approved by an Institutional Review Board (Medizinische Hochshule Hannover Carl-Neuberg-Strasse 1, 30625 Hannover, Germany). The study was conducted at a single center (Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany) in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. The study was registered in the Clinical Trials (NCT02154334) and EudraCT (2014‐000534‐38) registries.

Consent to Participate

Written informed consent was obtained from each participant before enrollment in the study after being advised of the potential risks and benefits of the study, as well as the investigational nature of the study.

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All authors provided final approval of the published version.

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Not applicable.

Author Contribution

All authors participated in the study design and implementation and/or conduct of the study. All authors read and approved the final manuscript.

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The original online version of this article was revised to correct Table 1 footnote.

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Zannikos, P., Solanki, B., De Meulder, M. et al. Pharmacokinetics of Nasal Esketamine in Patients with Allergic Rhinitis with and Without Nasal Decongestant Pretreatment and in Healthy Subjects with and Without Nasal Corticosteroid Pretreatment. Clin Pharmacokinet 62, 1315–1328 (2023). https://doi.org/10.1007/s40262-023-01273-z

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