{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:55:44Z","timestamp":1790506544936,"version":"4.1.0"},"reference-count":42,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T00:00:00Z","timestamp":1476835200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>\n                    AZD3293 (LY3314814) is a\u00a0promising new potentially disease-modifying BACE1 (\u03b2-secretase) inhibitor in Phase\u00a0III clinical development for the treatment of Alzheimer\u2019s disease. Reported here are the first two Phase\u00a0I studies: (1) a\u00a0single ascending dose study evaluating doses of 1\u2013750\u200amg with a\u00a0food-effect component (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u200a=\u200a72), and (2) a\u00a02-week multiple ascending dose study evaluating doses of 15 or 50\u200amg once daily (QD) or 70\u200amg once weekly (QW) in elderly subjects (Part\u00a01,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u200a=\u200a31), and 15, 50, or 150\u200amg QD in patients with mild to moderate Alzheimer\u2019s disease (Part\u00a02,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u200a=\u200a16). AZD3293 was generally well tolerated up to the highest doses given. No notable food effects were observed. PK following multiple doses (Part\u00a02) were t\n                    <jats:sub>max<\/jats:sub>\n                    of 1 to 3\u200ah and mean t\n                    <jats:sub>1\/2<\/jats:sub>\n                    of 16 to 21\u200ah across the 15 to 150\u200amg dose range. For single doses of \u22655\u200amg, a\u00a0\u226570% reduction was observed in mean plasma A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    and A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    concentrations, with prolonged suppression for up to 3\u00a0weeks at the highest dose level studied. Following multiple doses, robust reductions in plasma (\u226564% at 15\u200amg and \u226578% at \u226550\u200amg) and cerebrospinal fluid (\u226551% at 15\u200amg and \u226576% at \u226550\u200amg) A\u03b2 peptides were seen, including prolonged suppression even with a\u00a0QW dosing regimen. AZD3293 is the only BACE1 inhibitor for which prolonged suppression of plasma A\u03b2 with a\u00a0QW dosing schedule has been reported. Two Phase\u00a0III studies of AZD3293 (AMARANTH, NCT02245737; and DAYBREAK-ALZ, NCT02783573) are now ongoing.\n                  <\/jats:p>","DOI":"10.3233\/jad-160701","type":"journal-article","created":{"date-parts":[[2016,10,21]],"date-time":"2016-10-21T11:29:56Z","timestamp":1477049396000},"page":"1039-1053","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":81,"title":["AZD3293: Pharmacokinetic and\u00a0Pharmacodynamic Effects in\u00a0Healthy\u00a0Subjects and Patients with\u00a0Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"55","author":[{"given":"Gvido","family":"Cebers","sequence":"first","affiliation":[{"name":"AstraZeneca, Neuroscience, Waltham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Alexander","sequence":"additional","affiliation":[{"name":"AstraZeneca, Neuroscience, Waltham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha Budd","family":"Haeberlein","sequence":"additional","affiliation":[{"name":"AstraZeneca, Neuroscience, Waltham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Han","sequence":"additional","affiliation":[{"name":"Early Phase Clinical Unit","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Goldwater","sequence":"additional","affiliation":[{"name":"Harbor Hospital","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Ereshefsky","sequence":"additional","affiliation":[{"name":"Early Phase Clinical Unit","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Olsson","sequence":"additional","affiliation":[{"name":"AstraZeneca, Neuroscience, Waltham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naidong","family":"Ye","sequence":"additional","affiliation":[{"name":"AstraZeneca, Neuroscience, Waltham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rosen","sequence":"additional","affiliation":[{"name":"AstraZeneca, Neuroscience, Waltham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muir","family":"Russell","sequence":"additional","affiliation":[{"name":"AstraZeneca, Protein Biomarkers, Personalised Healthcare and Biomarkers, Alderley Park, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Maltby","sequence":"additional","affiliation":[{"name":"AstraZeneca, Protein Biomarkers, Personalised Healthcare and Biomarkers, Alderley Park, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Eketj\u00e4ll","sequence":"additional","affiliation":[{"name":"Karolinska Institutet","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Kugler","sequence":"additional","affiliation":[{"name":"AstraZeneca, Neuroscience, Waltham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,10,19]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"Dementia. 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