{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:04:29Z","timestamp":1790795069942,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,8,25]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">CSL<\/jats:styled-content>\n              112 is a new formulation of human apolipoprotein A\u2010I (apoA\u2010I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double\u2010blind, multicenter, dose\u2010ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics\/pharmacodynamics of a\n              <jats:styled-content style=\"fixed-case\">CSL<\/jats:styled-content>\n              112 infusion among patients with stable atherosclerotic disease.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Patients were randomized to single ascending doses of\n              <jats:styled-content style=\"fixed-case\">CSL<\/jats:styled-content>\n              112 (1.7, 3.4, or 6.8\u00a0g) or placebo, administered over a 2\u2010hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations &gt;3\u00d7 upper limits of normal and study drug\u2013related adverse events. Pharmacokinetic\/pharmacodynamic assessments included apoA\u2010I plasma concentration and measures of the ability of serum to promote cholesterol efflux from cells ex\u00a0vivo. Of 45 patients randomized, 7, 12, and 14 received 1.7\u2010, 3.4\u2010, and 6.8\u2010g\n              <jats:styled-content style=\"fixed-case\">CSL<\/jats:styled-content>\n              112, respectively, and 11 received placebo. There were no clinically significant elevations (&gt;3\u00d7 upper limit of normal) in alanine aminotransferase or aspartate aminotransferase. Adverse events were nonserious and mild and occurred in 5 (71%), 5 (41%), and 6 (43%) patients in the\n              <jats:styled-content style=\"fixed-case\">CSL<\/jats:styled-content>\n              112 1.7\u2010, 3.4\u2010, and 6.8\u2010g groups, respectively, compared with 3 (27%) placebo patients. The imbalance in adverse events was attributable to vessel puncture\/infusion\u2010site bruising.\n              <jats:styled-content style=\"fixed-case\">CSL<\/jats:styled-content>\n              112 resulted in rapid (\n              <jats:italic>T<\/jats:italic>\n              <jats:sub>max<\/jats:sub>\n              \u22482\u00a0hours) and dose\u2010dependent increases in apoA\u2010I (145% increase in the 6.8\u2010g group) and total cholesterol efflux (up to 3.1\u2010fold higher than placebo) (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">CSL<\/jats:styled-content>\n              112 infusion was well tolerated in patients with stable atherosclerotic disease.\n              <jats:styled-content style=\"fixed-case\">CSL<\/jats:styled-content>\n              112 immediately raised apoA\u2010I levels and caused a rapid and marked increase in the capacity of serum to efflux cholesterol. This potential novel approach for the treatment of atherosclerosis warrants further investigation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Clinical Trial Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">URL<\/jats:styled-content>\n              :\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.ClinicalTrials.gov\">http:\/\/www.ClinicalTrials.gov<\/jats:ext-link>\n              . Unique identifier:\n              <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>\n              01499420.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.115.002171","type":"journal-article","created":{"date-parts":[[2015,8,26]],"date-time":"2015-08-26T01:04:31Z","timestamp":1440551071000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":100,"title":["Infusion of Reconstituted High\u2010Density Lipoprotein, CSL112, in Patients With Atherosclerosis: Safety and Pharmacokinetic Results From a Phase 2a Randomized Clinical Trial"],"prefix":"10.1161","volume":"4","author":[{"given":"Pierluigi","family":"Tricoci","sequence":"first","affiliation":[{"name":"Duke Clinical Research Institute, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise M.","family":"D'Andrea","sequence":"additional","affiliation":[{"name":"CSL Behring, King of Prussia, 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