{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:23:29Z","timestamp":1792794209932,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":40,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Osmotica Pharmaceuticals Inc.","id":[{"id":"https:\/\/ror.org\/03re7j391","id-type":"ROR","asserted-by":"crossref"}]},{"name":"RVL Pharmaceuticals"},{"name":"Premier Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Baclofen, a racemic \u03b3-aminobutyric acid B receptor agonist, is commonly used for the management of multiple sclerosis\u2013related spasticity but is associated with frequent dosing and poor tolerability. Arbaclofen, the active R-enantiomer of baclofen, exhibits 100- to 1000-fold greater specificity for the \u03b3-aminobutyric acid B receptor compared with the S-enantiomer and \u223c5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets allow a dosing interval of 12\u2005h and have shown a favourable safety and efficacy profile in early clinical development. A 12-week, randomized, placebo-controlled Phase 3 trial in adults with multiple sclerosis\u2013related spasticity demonstrated that arbaclofen extended-release 40\u2005mg\/day significantly reduced spasticity symptoms compared with placebo and was safe and well tolerated. The current study is an open-label extension of the Phase 3 trial designed to evaluate the long-term safety and efficacy of arbaclofen extended-release. In a 52-week, open-label, multicentre study, adults with a Total Numeric-transformed Modified Ashworth Scale score \u22652 in the most affected limb received oral arbaclofen extended-release titrated over 9 days up to 80\u2005mg\/day based on tolerability. The primary objective was assessment of arbaclofen extended-release safety and tolerability. Secondary objectives included an assessment of efficacy using the Total Numeric-transformed Modified Ashworth Scale-most affected limb, the Patient Global Impression of Change and Expanded Disability Status Scale. Of 323 patients enrolled, 218 (67.5%) completed 1 year of treatment. Most patients (74.0%) achieved an arbaclofen extended-release maintenance dose of 80\u2005mg\/day. At least one treatment-emergent adverse event was reported by 278 patients (86.1%). The most common adverse events were [n patients (%)]: urinary tract disorder [112 (34.7)], muscle weakness [77 (23.8)], asthenia [61 (18.9)], nausea [70 (21.7)], dizziness [52 (16.1)], somnolence [41 (12.7)], vomiting [29 (9.0)], headache [24 (7.4)] and gait disturbance [20 (6.2)]. Most adverse events were of mild\u2013moderate severity. Twenty-eight serious adverse events were reported. One death occurred during the study, a myocardial infarction that was considered by investigators as unlikely to be related to treatment. Overall, 14.9% of patients discontinued due to adverse events, primarily muscle weakness, multiple sclerosis relapse, asthenia and nausea. Evidence of improvement in multiple sclerosis\u2013related spasticity was observed across arbaclofen extended-release dosages. Arbaclofen extended-release treatment (up to 80\u2005mg\/day) was well tolerated and reduced symptoms of spasticity in adult patients with multiple sclerosis for 1 year.<\/jats:p>\n                  <jats:p>Clinical Trial Identifier: ClinicalTrials.gov, NCT03319732<\/jats:p>","DOI":"10.1093\/braincomms\/fcad026","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T06:29:18Z","timestamp":1675751358000},"source":"Crossref","is-referenced-by-count":3,"title":["Arbaclofen extended-release tablets for spasticity in multiple sclerosis: open-label extension study"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6499-1523","authenticated-orcid":false,"given":"Darin T","family":"Okuda","sequence":"first","affiliation":[{"name":"The University of Texas Southwestern Medical Center , Dallas, TX 75390-8806 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kantor","sequence":"additional","affiliation":[{"name":"Florida Atlantic University , Boca Raton, FL 33431 , USA"},{"name":"Nova Southeastern University , Fort Lauderdale, FL 33314 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Jaros","sequence":"additional","affiliation":[{"name":"Summit Analytical , Denver, CO 80238 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"deVries","sequence":"additional","affiliation":[{"name":"RVL Pharmaceuticals, Inc. , Bridgewater, NJ 08807 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Hunter","sequence":"additional","affiliation":[{"name":"Advanced Neuroscience Institute , Franklin, TN 37064 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"issue":"2 Suppl","key":"2023022702545765000_","first-page":"S15","article-title":"Overview of the epidemiology, diagnosis, and disease progression associated with multiple sclerosis","volume":"19","author":"Tullman","year":"2013","journal-title":"Am J Manag Care"},{"issue":"10","key":"2023022702545765000_","doi-asserted-by":"crossref","first-page":"e1029","DOI":"10.1212\/WNL.0000000000007035","article-title":"The prevalence of MS in the United States: A population-based estimate using health claims data","volume":"92","author":"Wallin","year":"2019","journal-title":"Neurology"},{"issue":"10","key":"2023022702545765000_","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s11910-019-0991-2","article-title":"Assessment and measurement of spasticity in MS: State of the evidence","volume":"19","author":"Hugos","year":"2019","journal-title":"Curr Neurol Neurosci Rep"},{"key":"2023022702545765000_","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s40271-016-0173-0","article-title":"A cross-sectional study of the impact of spasticity on daily activities in multiple sclerosis","volume":"9","author":"Bethoux","year":"2016","journal-title":"Patient"},{"issue":"5","key":"2023022702545765000_","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1191\/1352458504ms1085oa","article-title":"Prevalence and treatment of spasticity reported by multiple sclerosis patients","volume":"10","author":"Rizzo","year":"2004","journal-title":"Mult Scler"},{"key":"2023022702545765000_","article-title":"Non-pharmacological interventions for spasticity in multiple sclerosis","volume":"2","author":"Amatya","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"issue":"4","key":"2023022702545765000_","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.pmr.2013.07.003","article-title":"Spasticity management in multiple sclerosis","volume":"24","author":"Hughes","year":"2013","journal-title":"Phys Med Rehabil Clin N Am"},{"issue":"2","key":"2023022702545765000_","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1159\/000095699","article-title":"Symptomatic treatment of multiple sclerosis. 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