{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:25:48Z","timestamp":1792729548601,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T00:00:00Z","timestamp":1510185600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>We are developing a second generation 8\u2010OH quinoline (2\u2010(dimethylamino) methyl\u20105, 7\u2010dichloro\u20108\u2010hydroxyquinoline [PBT2, Prana Biotechnology]) for targeting amyloid \u03b2 (A\u03b2) in Alzheimer's disease (AD). In an earlier phase IIa, 3\u00a0month trial, PBT2 lowered cerebrospinal fluid A\u03b2 by 13% and improved cognition (executive function) in a dose\u2010related fashion in early AD. We, therefore, sought to learn whether PBT2 could alter the A\u03b2\u2010PET signal in subjects with prodromal or mild AD, in an exploratory randomized study over a 12\u2010month phase in a double\u2010blind and a 12\u2010month open label extension phase trial design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>For inclusion, the usual clinical criteria for prodromal or probable AD, Mini\u2013Mental State Examination \u226520, and global Pittsburgh compound B (PiB)\u2010PET standardized uptake volume ratio (SUVR) &gt;1.7 were used. As this was an exploratory study, we included contemporaneous matched control data from the Australian Imaging Biomarker and Lifestyle Study (AIBL). Other measures included fluorodeoxyglucose\u2010positron emission tomography, magnetic resonance imaging volumetrics, blood A\u03b2 biomarkers, and cognition and function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forty subjects completed the first 12\u2010month double\u2010blind phase (placebo\u00a0=\u00a015, PBT2\u00a0=\u00a025), and 27 subjects completed the 12\u2010month open label extension phase (placebo\u00a0=\u00a011, PBT2\u00a0=\u00a016). Overall, PTB2 250\u00a0mg\/day was safe and well tolerated. The mean PiB\u2010PET SUVR at baseline was 2.51\u00a0\u00b1\u00a00.59. After adjusting for baseline SUVR, in the double\u2010blind phase, the placebo group showed a nonsignificant decline in PiB\u2010PET SUVR, whereas the PBT2 group declined significantly (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.048). Subjects who did not enter or complete the extension study had a significantly higher 12\u2010month\u00a0A\u03b2\u2010PET SUVR (2.68\u00a0\u00b1\u00a00.55) compared with those who completed (2.29\u00a0\u00b1\u00a00.48). Both groups differed significantly from the rate of change over 12\u00a0months in the AIBL control group. In the open label 12\u2010month extension study, the PiB\u2010SUVR stabilized. There were no significant differences between PBT2 and controls in fluorodeoxyglucose\u2010positron emission tomography, magnetic resonance imaging volumetrics, blood A\u03b2 biomarkers, or cognition\/function over the course of the double\u2010blind phase.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>There was no significant difference between PBT2 and controls at 12\u00a0months, likely due to the large individual variances over a relatively small number of subjects. PBT2 was associated with a significant 3% PiB\u2010PET SUVR decline in the double\u2010blind phase and a stabilization of SUVR in the open\u2010label phase. From this exploratory study, we have learned that the entry criterion of SUVR should have been set at \u2265 1.5 and\u00a0&lt;2.0, where we know from the AIBL study that subjects in this band are accumulating A\u03b2 in a linear fashion and that subjects who withdrew from this type of study have much higher SUVRs, which if not taken into account, could distort the final results. Because of large individual variations in SUVR, future studies of PBT2 will require larger numbers of subjects (n\u00a0&gt;\u00a090 per arm) over a longer period (18\u00a0months or more). Further evaluation of higher doses of PBT2 in earlier stages of AD is warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ACTRN 12611001008910 and ACTRN\u00a012613000777796.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.trci.2017.10.001","type":"journal-article","created":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T16:35:13Z","timestamp":1510245313000},"page":"622-635","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["A randomized, exploratory molecular imaging study targeting amyloid \u03b2 with a novel 8\u2010OH quinoline in Alzheimer's disease: The PBT2\u2010204 IMAGINE study"],"prefix":"10.1002","volume":"3","author":[{"given":"Victor L.","family":"Villemagne","sequence":"first","affiliation":[{"name":"Department of Molecular Imaging and Therapy (Research) Austin 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