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This was the first study of selisistat in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> patients and was primarily aimed at development of pharmacodynamic biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a randomized, double\u2010blind, placebo\u2010controlled, multicentre exploratory study. Fifty\u2010five male and female patients in early stage <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> were randomized to receive 10\u2009mg or 100\u2009mg of selisistat or placebo once daily for 14 days. Blood sampling, clinical and safety assessments were conducted throughout the study. Candidate pharmacodynamic markers included circulating soluble huntingtin and innate immune markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Selisistat was found to be safe and well tolerated, and systemic exposure parameters showed that the average steady\u2010state plasma concentration achieved at the 10\u2009mg dose level (125\u2009n<jats:sc>m<\/jats:sc>) was comparable with the <jats:styled-content style=\"fixed-case\">I<jats:italic>C<\/jats:italic><jats:sub>50<\/jats:sub><\/jats:styled-content> for <jats:styled-content style=\"fixed-case\">SirT1<\/jats:styled-content> inhibition. No adverse effects on motor, cognitive or functional readouts were recorded. While circulating levels of soluble huntingtin were not affected by selisistat in this study, the biological samples collected have allowed development of assay technology for use in future studies. No effects on innate immune markers were seen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Selisistat was found to be safe and well tolerated in early stage <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content> patients at plasma concentrations within the anticipated therapeutic concentration range.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12512","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T04:47:41Z","timestamp":1410842861000},"page":"465-476","source":"Crossref","is-referenced-by-count":163,"title":["An exploratory double\u2010blind, randomized clinical trial with selisistat, a <scp>SirT1<\/scp> inhibitor, in patients with <scp>H<\/scp>untington's disease"],"prefix":"10.1111","volume":"79","author":[{"given":"Sigurd D.","family":"S\u00fcssmuth","sequence":"first","affiliation":[{"name":"Department of Neurology Ulm University Hospital  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman","family":"Haider","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease University College London Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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