{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:36:50Z","timestamp":1790105810203,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T00:00:00Z","timestamp":1559779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>AG10 is a novel, potent, and selective oral transthyretin (TTR) stabilizer being developed to treat TTR amyloidosis (ATTR). This randomized, double\u2010blind, placebo\u2010controlled study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics (ex vivo stabilization) of orally administered AG10 in healthy adult volunteers. Both mutant and wild\u2010type ATTR are underdiagnosed diseases with limited therapeutic options. As TTR amyloidogenesis is initiated by dissociation of TTR tetramers destabilized due to inherited mutations or aging, AG10 is designed to treat the disease at its source. Four single and three multiple ascending dose levels of AG10 or matching placebo were orally administered. Safety and tolerability were assessed by vital signs, electrocardiogram, adverse events, and clinical laboratory tests. Pharmacokinetics were measured using a validated bioanalytical assay. Pharmacodynamics were assessed via three pharmacodynamic assays of TTR stabilization. AG10 was uniformly well tolerated, and no safety signals of clinical concern were observed. Pharmacokinetic observations included time to maximum concentration &lt;1\u00a0hour, dose\u2010dependent maximum concentration and area under the plasma concentration\u2013time curve, low intersubject variability, and half\u2010life \u223c25\u00a0hr. Complete (&gt;90%) stabilization of TTR was observed across the entire dosing interval at steady state on the highest dose tested. Serum TTR levels, an in vivo reflection of TTR stabilization by AG10, increased from baseline following 12 days of dosing. AG10 appears to be safe and well tolerated in healthy adult volunteers and can completely stabilize TTR across the dosing interval, establishing clinical proof of concept. Based on these data, AG10 has the potential to be a safe and effective treatment for patients with either mutant or wild\u2010type ATTR.<\/jats:p>","DOI":"10.1002\/cpdd.700","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T02:42:53Z","timestamp":1559875373000},"page":"115-129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["First\u2010in\u2010Human Study of AG10, a Novel, Oral, Specific, Selective, and Potent Transthyretin Stabilizer for the Treatment of Transthyretin Amyloidosis: A Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Adult Volunteers"],"prefix":"10.1002","volume":"9","author":[{"given":"Jonathan C.","family":"Fox","sequence":"first","affiliation":[{"name":"Eidos Therapeutics, Inc.  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Hellawell","sequence":"additional","affiliation":[{"name":"Eidos Therapeutics, Inc.  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Rao","sequence":"additional","affiliation":[{"name":"Eidos Therapeutics, Inc.  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"O'Reilly","sequence":"additional","affiliation":[{"name":"Celerion, Inc.  Tempe AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick","family":"Lumpkin","sequence":"additional","affiliation":[{"name":"Eidos Therapeutics, Inc.  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Jernelius","sequence":"additional","affiliation":[{"name":"Eidos Therapeutics, Inc.  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