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This was a phase 3, international, multicenter, randomized, 12-week, double-blind study, followed by a repeated treatment, open-label extension. Patients were aged 18\u201385\u00a0years with PSLLS (Modified Ashworth Scale [MAS]\u2009\u2265\u20093) of the ankle with the most recent stroke occurring\u2009\u2265\u20093\u00a0months before screening. Patients (double-blind phase) were randomized (<jats:italic>n<\/jats:italic>\u2009=\u2009468) to onabotulinumtoxinA 300\u2013400 U (300 U, mandatory ankle muscles (gastrocnemius, soleus, tibialis posterior); and\u2009\u2264\u2009100 U, optional lower limb muscles (flexor digitorum longus, flexor hallucis longus, flexor digitorum brevis, extensor hallucis, and rectus femoris]) or placebo. Primary endpoint: MAS change from baseline (average score of weeks 4 and 6). Secondary endpoints: physician-assessed Clinical Global Impression of Change (CGI) average score of weeks 4 and 6 and physician-assessed Goal Attainment Scale (GAS; active and passive, weeks 8 and 12). When stratified by time since stroke (\u2264\u200924\u00a0months, <jats:italic>n<\/jats:italic>\u2009=\u2009153;\u2009&gt;\u200924\u00a0months, <jats:italic>n<\/jats:italic>\u2009=\u2009315, post hoc), patients treated\u2009\u2264\u200924\u00a0months post-stroke experienced greater improvements from baseline versus placebo in MAS (\u2212\u20090.31 vs\u2009\u2212\u20090.17), CGI (0.49 vs 0.12), and passive GAS scores (week 12, 0.37 vs 0.26). A\u2009\u2265\u2009\u2009\u2212\u20091-point improvement in active (week 12; <jats:italic>p<\/jats:italic>\u2009=\u20090.04) and passive (week 8; <jats:italic>p<\/jats:italic>\u2009=\u20090.02) GAS scores versus placebo was achieved by more patients treated\u2009\u2264\u200924\u00a0months post-stroke; in patients treated\u2009&gt;\u200924\u00a0months post-stroke, improvements were only observed in active scores (week 8; <jats:italic>p<\/jats:italic>\u2009=\u20090.04). OnabotulinumtoxinA 300\u2013400 U was well tolerated, with no new safety findings.<\/jats:p>","DOI":"10.1007\/s00702-020-02251-6","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T03:03:00Z","timestamp":1603767780000},"page":"1619-1629","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Impact of early intervention with onabotulinumtoxinA treatment in adult patients with post-stroke lower limb spasticity: results from the double-blind, placebo-controlled, phase 3 REFLEX study"],"prefix":"10.1007","volume":"127","author":[{"given":"Atul T.","family":"Patel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony B.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Geis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang H.","family":"Jost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rozalina","family":"Dimitrova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,27]]},"reference":[{"key":"2251_CR1","unstructured":"Adis R&D Insight Drug pipeline database, Botulinum toxin A - Allergan. https:\/\/adisinsight.springer.com\/drugs\/800008810. 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Patel has received research grant support from Allergan plc, Merz, and Ipsen, and speaking honoraria from Merz and Allergan plc. Anthony B. Ward is a speaker and consultant for Allergan plc, Ipsen, and Merz. Carolyn Geis has received research support from and is a speaker\/consultant for Allergan plc. Wolfgang H. Jost is a speaker and consultant for Allergan plc, Ipsen, and Merz. Chengcheng Liu and Rozalina Dimitrova are employees of Allergan plc.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}