@article{683120419e0a42359647b9c073df9681,
title = "A randomized phase 2b efficacy study in patients with seizure episodes with a predictable pattern using Staccato{\textregistered} alprazolam for rapid seizure termination",
abstract = "Objective: Alprazolam administered via the Staccato{\textregistered} breath-actuated device is delivered into the deep lung for rapid systemic exposure and is a potential therapy for rapid epileptic seizure termination (REST). We conducted an inpatient study (ENGAGE-E-001 [NCT03478982]) in patients with stereotypic seizure episodes with prolonged or repetitive seizures to determine whether Staccato alprazolam rapidly terminates seizures in a small observed population after administration under direct supervision. Methods: Adult patients with established diagnosis of focal and/or generalized epilepsy with a documented history of seizure episodes with a predictable pattern were enrolled. They were randomized 1:1:1 to double-blind treatment of a single seizure event with one dose of Staccato alprazolam 1.0 mg or 2.0 mg, or Staccato placebo in an inpatient unit. The primary end point of the study was the proportion of responders in each treatment group achieving seizure activity cessation within 2 min after administration of study drug and no recurrence of seizure activity within 2 h. Results: A total of 273 patients were screened, and 116 randomized patients received treatment with the study drug in the double-blind part. The proportion of treated patients who were responders was 65.8% for each of Staccato alprazolam 1.0 mg (n = 38; p =.0392) and 2.0 mg (n = 38; p =.0392), compared with 42.5% for Staccato placebo (n = 40). Staccato alprazolam was well tolerated when administered as a single dose of 1.0 or 2.0 mg: cough and somnolence were the most common adverse events (AEs) (both 14.5%), followed by dysgeusia (13.2%). AEs were mostly mild or moderate in intensity; there were no treatment-related serious AEs. Significance: Both 1.0 mg and 2.0 mg doses of Staccato alprazolam demonstrated efficacy in rapidly terminating seizures in an inpatient setting and were well tolerated. The next step is a Phase 3 confirmatory study to demonstrate efficacy and safety of Staccato alprazolam for rapid cessation of seizures in an outpatient setting.",
keywords = "acute treatment, alprazolam, clinical trial, deep lung delivery, epilepsy, rapid onset, seizure",
author = "Jacqueline French and Victor Biton and Hina Dave and Kamil Detyniecki and Gelfand, {Michael A.} and Hui Gong and Kore Liow and O'Brien, {Terence J.} and Ahmed Sadek and Bree DiVentura and Brittany Reich and Jouko Isojarvi",
note = "Funding Information: This article is dedicated to the memory of our friend and colleague Dr. Jouko Isojarvi. Jouko was passionate about epilepsy research and drug development and will be remembered as a clinician and scientist who made a difference in the lives of people living with epilepsy. The authors thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study (see Appendix S1, Investigator appendix, in the Supporting Information). The authors developed the first draft of the manuscript and approved the content of the final version. The authors would like to acknowledge Ciara Duffy, PhD, CMPP (Evidence Scientific Solutions, Sydney, Australia) and Leonard Wills, BSc(Hons) (Evidence Scientific Solutions, London, UK), who were involved in helping with the creation of the manuscript from Draft 2 onwards. Their role included coordinating the author review process; incorporation of comments provided by the authors; editing and formatting the text; production of original figures; formatting of tables and figures; verifying the accuracy of the data; verifying the accuracy of references; collecting author contribution and conflict of interest statements; and assisting with the online submission process by uploading files, which was funded by UCB Pharma. Publication coordination was provided by Tom Grant, PhD (UCB Pharma, Slough, UK). Brittany Reich was an employee of Engage Therapeutics, Inc., at the time that this study was conducted and is currently affiliated with UCB Pharma. Jouko Isojarvi was an employee of Engage Therapeutics, Inc., at the time this study was conducted, and was contracted by UCB Pharma and affiliated with ASD Consulting LLC during the article's development. Funding Information: This article is dedicated to the memory of our friend and colleague Dr. Jouko Isojarvi. Jouko was passionate about epilepsy research and drug development and will be remembered as a clinician and scientist who made a difference in the lives of people living with epilepsy. The authors thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study (see Appendix S1 , Investigator appendix, in the Supporting Information ). The authors developed the first draft of the manuscript and approved the content of the final version. The authors would like to acknowledge Ciara Duffy, PhD, CMPP (Evidence Scientific Solutions, Sydney, Australia) and Leonard Wills, BSc(Hons) (Evidence Scientific Solutions, London, UK), who were involved in helping with the creation of the manuscript from Draft 2 onwards. Their role included coordinating the author review process; incorporation of comments provided by the authors; editing and formatting the text; production of original figures; formatting of tables and figures; verifying the accuracy of the data; verifying the accuracy of references; collecting author contribution and conflict of interest statements; and assisting with the online submission process by uploading files, which was funded by UCB Pharma. Publication coordination was provided by Tom Grant, PhD (UCB Pharma, Slough, UK). Brittany Reich was an employee of Engage Therapeutics, Inc., at the time that this study was conducted and is currently affiliated with UCB Pharma. Jouko Isojarvi was an employee of Engage Therapeutics, Inc., at the time this study was conducted, and was contracted by UCB Pharma and affiliated with ASD Consulting LLC during the article's development. Publisher Copyright: {\textcopyright} 2022 Engage Therapeutics. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.",
year = "2023",
month = feb,
doi = "10.1111/epi.17441",
language = "English (US)",
volume = "64",
pages = "374--385",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "2",
}