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CathA was recently discovered as a target for heart failure, fostering the development of CathA inhibitors with SAR164653 as a frontrunner. The first\u2010in\u2010man study investigated single oral doses from 20 to 800\u2009mg of SAR164653 followed by repeat dose studies at doses up to 800\u2009mg in healthy young and elderly subjects. SAR164653 was safe and well tolerated at doses up to 800\u2009mg in healthy subjects, and a maximum tolerated dose could not be determined from the study. Activity of \u00df\u2010galactosidase measured in leukocytes did not show any abnormalities. The t<jats:sub>max<\/jats:sub> was 1.0 to 2.5 hours, and the t<jats:sub>1\/2<\/jats:sub> was \u223c5\u201311 after single dosing; exposure increased less than dose proportional. Following multiple dosing, accumulation was not observed, C<jats:sub>max<\/jats:sub> and AUC<jats:sub>0\u201324<\/jats:sub> increased in a dose\u2010proportional manner, and t<jats:sub>1\/2<\/jats:sub> was around 14\u201320 hours. The novel CathA inhibitor SAR164653 was found to have a favorable safety profile in these early phase 1 studies, but further studies are required to confirm if SAR164653 is equally safe in patients undergoing long\u2010term treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cpdd.201","type":"journal-article","created":{"date-parts":[[2015,5,7]],"date-time":"2015-05-07T23:15:49Z","timestamp":1431040549000},"page":"57-68","source":"Crossref","is-referenced-by-count":14,"title":["Tolerability, safety, and pharmacokinetics of the novel cathepsin A inhibitor SAR164653 in healthy subjects"],"prefix":"10.1002","volume":"5","author":[{"given":"Joachim","family":"Tillner","sequence":"first","affiliation":[{"name":"Sanofi\u2010Aventis Deutschland Frankfurt a.M. Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Sanofi\u2010Aventis Deutschland Frankfurt a.M. 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