{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T16:26:48Z","timestamp":1764174408099,"version":"3.41.2"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,25]],"date-time":"2017-11-25T00:00:00Z","timestamp":1511568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Two multiple\u2010dose phase II studies were conducted in subjects with primary hypercholesterolemia to evaluate the LDL\u2010C lowering efficacy, safety, and tolerability of bococizumab, a proprotein convertase subtilisin\/kexin type 9 (PCSK9) inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The results from the two phase II, double\u2010blinded, randomized, placebo\u2010controlled, multicenter studies conducted in the USA and Canada were combined. In Study 1, 90 subjects with LDL\u2010C \u2265100\u00a0mg\/dL received intravenous (IV) placebo or bococizumab 0.25, 1, 3, or 6\u00a0mg\/kg. In Study 2, 45 subjects with LDL\u2010C \u226580\u00a0mg\/dL received IV placebo or bococizumab 1 or 3\u00a0mg\/kg. Subjects were treated every 4\u00a0weeks for 12\u00a0weeks. Dosing was interrupted if LDL\u2010C dipped to \u226425\u00a0mg\/dL and resumed if LDL\u2010C returned to \u226540\u00a0mg\/dL. The primary endpoint was percent LDL\u2010C reduction from baseline at Week 12.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At Week 12, the reductions from baseline in LDL\u2010C vs placebo in the bococizumab 0.25, 1, 3, and 6\u00a0mg\/kg groups were 9.3%, 10.2%, 41.6%, and 52.0%, respectively (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>.001 vs placebo for all). LDL\u2010C reductions were greater (69.9%) in subjects who received all three doses of bococizumab 6\u00a0mg\/kg (<jats:italic>P\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>.001 vs placebo). Pharmacogenomic analysis revealed that 15% of hyperlipidemic subjects carried polymorphisms associated with familial hypercholesterolemia, with maximal LDL\u2010C reductions being similar between carriers and noncarriers. Adverse events were mild, unrelated to bococizumab, and resolved by Week 12.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These studies demonstrated that bococizumab safely and effectively lowered LDL\u2010C in hypercholesterolemic subjects on high doses of statin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12308","type":"journal-article","created":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T07:32:44Z","timestamp":1508743964000},"source":"Crossref","is-referenced-by-count":14,"title":["Effects of 12\u00a0weeks of treatment with intravenously administered bococizumab, a humanized monoclonal antibody blocking proprotein convertase subtilisin\/kexin type 9, in hypercholesterolemic subjects on high\u2010dose statin"],"prefix":"10.1111","volume":"36","author":[{"given":"Sergio","family":"Fazio","sequence":"first","affiliation":[{"name":"The Knight Cardiovascular Institute Oregon Health and Science University  Portland OR USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Atlanta Diabetes Associates  Atlanta GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tenshang","family":"Joh","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  South San Francisco and San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Wan","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  South San Francisco and San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Riel","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  South San Francisco and San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Forgues","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  South San Francisco and San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles M.","family":"Baum","sequence":"additional","affiliation":[{"name":"Mirati Therapeutics Inc.  San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela D.","family":"Garzone","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  South San Francisco and San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0761-289X","authenticated-orcid":false,"given":"Barry","family":"Gumbiner","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  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