Stuart Madden, Leslie Citrome, Christoph U Correll, Evelyn K Shih, Miguel Lopez-Toledano, Adrian L Rabinowicz, Enrique Carrazana
{"title":"A Single-Dose, Randomized, Open-Label, Parallel Design Study to Characterize the Pharmacokinetics of an Investigational Olanzapine Intranasal Spray Compared to a Reference Dose of Olanzapine Intramuscular Injection in Healthy Adult Males.","authors":"Stuart Madden, Leslie Citrome, Christoph U Correll, Evelyn K Shih, Miguel Lopez-Toledano, Adrian L Rabinowicz, Enrique Carrazana","doi":"10.4088/JCP.24m15665","DOIUrl":null,"url":null,"abstract":"<p><p><b>Objective:</b> Injectable olanzapine for acute agitation in psychiatric disorders is limited to delivery by health care professionals in supervised settings. Intranasal (IN) administration offers a potential needle free route of delivery with favorable pharmacokinetics and patient experience, including the possibility of self-administration in community settings. Two IN formulations of olanzapine containing the permeation enhancer dodecyl maltoside (DDM) were assessed, with intramuscular (IM) olanzapine as a reference.</p><p><p><b>Methods:</b> In this randomized phase 1 trial (conducted October 2023), healthy volunteers (N =24) were randomized 1:1: 1 to receive 1 dose of IN olanzapine 7.5 mg+0.25% DDM, IN olanzapine 7.5 mg+0.50% DDM, or olanzapine 7.5 mg IM. Plasma olanzapine concentrations were measured over time, and safety and tolerability were assessed.</p><p><p><b>Results:</b> Mean peak plasma olanzapine concentrations were 31.5, 32.3, and 20.5 ng/mL for 0.25% and 0.50% DDM sprays and IM dosing, respectively. Median times to peak plasma concentration were 4.8, 10.2, and 37.8 minutes. After a single dose of the 0.25% and 0.50% DDM formulations, bioavailability was 88.8% and 83.3% of a single IM dose. All reported treatment emergent adverse events were mild, transient, and deemed possibly related to the study drug, with the most frequent being sedation (n = 24) and nasal discomfort lasting seconds (n = 16, IN treatments). Nasal irritation scores were grade 0 (no sign of nasal irritation or mucosal erosion), and suicide risk assessment was negative for all time points.</p><p><p><b>Conclusion:</b> Two novel investigational IN formulations of olanzapine containing the permeation enhancer DDM showed favorable pharmacokinetics and an acceptable safety profile presenting no unexpected signals in healthy adults. Continued study is warranted.</p><p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT06600477.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 2","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4088/JCP.24m15665","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
A Single-Dose, Randomized, Open-Label, Parallel Design Study to Characterize the Pharmacokinetics of an Investigational Olanzapine Intranasal Spray Compared to a Reference Dose of Olanzapine Intramuscular Injection in Healthy Adult Males.
Objective: Injectable olanzapine for acute agitation in psychiatric disorders is limited to delivery by health care professionals in supervised settings. Intranasal (IN) administration offers a potential needle free route of delivery with favorable pharmacokinetics and patient experience, including the possibility of self-administration in community settings. Two IN formulations of olanzapine containing the permeation enhancer dodecyl maltoside (DDM) were assessed, with intramuscular (IM) olanzapine as a reference.
Methods: In this randomized phase 1 trial (conducted October 2023), healthy volunteers (N =24) were randomized 1:1: 1 to receive 1 dose of IN olanzapine 7.5 mg+0.25% DDM, IN olanzapine 7.5 mg+0.50% DDM, or olanzapine 7.5 mg IM. Plasma olanzapine concentrations were measured over time, and safety and tolerability were assessed.
Results: Mean peak plasma olanzapine concentrations were 31.5, 32.3, and 20.5 ng/mL for 0.25% and 0.50% DDM sprays and IM dosing, respectively. Median times to peak plasma concentration were 4.8, 10.2, and 37.8 minutes. After a single dose of the 0.25% and 0.50% DDM formulations, bioavailability was 88.8% and 83.3% of a single IM dose. All reported treatment emergent adverse events were mild, transient, and deemed possibly related to the study drug, with the most frequent being sedation (n = 24) and nasal discomfort lasting seconds (n = 16, IN treatments). Nasal irritation scores were grade 0 (no sign of nasal irritation or mucosal erosion), and suicide risk assessment was negative for all time points.
Conclusion: Two novel investigational IN formulations of olanzapine containing the permeation enhancer DDM showed favorable pharmacokinetics and an acceptable safety profile presenting no unexpected signals in healthy adults. Continued study is warranted.
期刊介绍：
For over 75 years, The Journal of Clinical Psychiatry has been a leading source of peer-reviewed articles offering the latest information on mental health topics to psychiatrists and other medical professionals.The Journal of Clinical Psychiatry is the leading psychiatric resource for clinical information and covers disorders including depression, bipolar disorder, schizophrenia, anxiety, addiction, posttraumatic stress disorder, and attention-deficit/hyperactivity disorder while exploring the newest advances in diagnosis and treatment.
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