{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T09:24:16Z","timestamp":1769851456213,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T00:00:00Z","timestamp":1642896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Reducing the peripheral absolute lymphocyte count (ALC) is a promising therapeutic approach in treating autoimmune diseases. LC51\u20100255 is a sphingosine\u20101\u2010phosphate 1 receptor modulator, which is known to decrease the peripheral ALC. We aimed to assess the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability profiles of LC51\u20100255 after a single oral administration in healthy subjects. A randomized, double\u2010blind, placebo\u2010controlled, dose\u2010escalation study was conducted in 50 healthy subjects. Each subject orally received LC51\u20100255 (0.25, 0.5, 1, 2, or 4\u00a0mg) or its matching placebo in an 8:2 ratio. Blood and urine samples were collected to assess the PKs, and PDs was evaluated using peripheral ALC and 24\u2010h hourly heart rate data. Safety and tolerability were assessed by monitoring treatment emergent adverse events (TEAEs), vital signs, 12\u2010lead electrocardiogram (ECG), continuous 24\u2010h ECG (via Holter monitoring), clinical laboratory tests, ophthalmologic tests, pulmonary function tests, and physical examinations. A single dose of LC51\u20100255 reduced ALC and heart rate in a reversible and dose\u2010dependent manner. Systemic exposure of LC51\u20100255 increased dose\u2010dependently and its half\u2010life ranged from 72.2 to 134.0\u00a0h. ALC and the systemic exposure of LC51\u20100255 seemed to be negatively correlated. LC51\u20100255 was well\u2010tolerated up to 2\u00a0mg, and the most common TEAE was bradycardia. The results of this study suggest that LC51\u20100255 can be developed into a beneficial treatment option for autoimmune disease.<\/jats:p>","DOI":"10.1111\/cts.13227","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T18:24:05Z","timestamp":1642616645000},"page":"1074-1083","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Single\u2010dose of LC51\u20100255, a selective S1P<sub>1<\/sub>receptor modulator, showed dose\u2010dependent and reversible reduction of absolute lymphocyte count in humans"],"prefix":"10.1111","volume":"15","author":[{"given":"Sang","family":"Won Lee","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Hanyang University Seoul Hospital Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inyoung","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaeseong","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SeungHwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u2010Jin","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung\u2010Sang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,1,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1997.4412"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804647"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70305-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20797"},{"key":"e_1_2_8_6_1","first-page":"S21","article-title":"A review of current and emerging therapeutic strategies in multiple sclerosis","volume":"19","author":"Tullman MJ","year":"2013","journal-title":"Am J Manag Care"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.04.006"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01622.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075011"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02284"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311743200"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70049-3"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.244"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","unstructured":"OlsonA HartungJ TimonyG et al.Safety and tolerability of orally administered RPC1063 a novel S1P1 receptor modulator in healthy adult volunteers results of a phase 1 study (P01:178). 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