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Variables were clinical outcome measures, Fridericia\u2010corrected QT (QTcF) duration, and pharmacodynamic (PD) biomarkers. Exposure metrics were area under the plasma concentration time curve (AUC) and maximum plasma concentration (C<jats:sub>max<\/jats:sub>), with a sigmoid E<jats:sub>max<\/jats:sub> model applied. Significant improvement in clinical efficacy outcomes was observed after 24 weeks of daily dosing. The primary outcome, time to stand from supine velocity, exhibited the highest sensitivity to vamorolone, with the lowest AUC value providing 50% of maximum effect (E<jats:sub>50<\/jats:sub>\u00a0=\u00a0186 ng\u00b7h\/mL), followed by time to climb 4 stairs (E<jats:sub>50<\/jats:sub>\u00a0=\u00a0478 ng\u00b7h\/mL), time to run\/walk 10 m (E<jats:sub>50<\/jats:sub>\u00a0=\u00a01220 ng\u00b7h\/mL), and 6\u2010minute walk test (E<jats:sub>50<\/jats:sub>\u00a0=\u00a01770 ng\u00b7h\/mL). Week 2 changes of proinflammatory PD biomarkers showed exposure\u2010dependent decreases. The E<jats:sub>50<\/jats:sub> was 260 ng\u00b7h\/mL for insulin\u2010like growth factor\u2010binding protein 2, 1200 ng\u00b7h\/mL for matrix metalloproteinase 12, 1260 ng\u00b7h\/mL for lymphotoxin \u03b11\/\u03b22, 1340 ng\u00b7h\/mL for CD23, 1420 ng\u00b7h\/mL for interleukin\u201022\u2010binding protein, and 1600 ng\u00b7h\/mL for macrophage\u2010derived chemokine\/C\u2010C motif chemokine 22. No relationship was found between QTcF interval changes from baseline and C<jats:sub>max<\/jats:sub> in week 2 or 24. This analysis showed that improvements in clinical efficacy end points in week 24 and PD biomarkers in week 2 were achieved at typical vamorolone exposure of 2 mg\/kg daily dose with a median AUC dose of 6 mg\/kg (3651 ng\u00b7h\/mL), corresponding to approximately 95% of maximum effects for most response variables.<\/jats:p>","DOI":"10.1002\/jcph.1632","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T22:15:07Z","timestamp":1590012907000},"page":"1385-1396","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Exposure\u2010Response Analysis of Vamorolone (VBP15) in Boys With Duchenne Muscular Dystrophy"],"prefix":"10.1002","volume":"60","author":[{"given":"Xiaonan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University at Buffalo State University of New York  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurie S.","family":"Conklin","sequence":"additional","affiliation":[{"name":"ReveraGen BioPharma  Rockville Maryland USA"},{"name":"Children's National Hospital  Washington District of Columbia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"van den Anker","sequence":"additional","affiliation":[{"name":"ReveraGen BioPharma  Rockville Maryland USA"},{"name":"Children's National Hospital  Washington District of Columbia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric P.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"ReveraGen BioPharma  Rockville Maryland USA"},{"name":"Binghamton University\u2013SUNY  Binghamton New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula R.","family":"Clemens","sequence":"additional","affiliation":[{"name":"University of Pittsburgh and Department of Veterans Affairs Medical Center  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4027-0550","authenticated-orcid":false,"given":"William J.","family":"Jusko","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University at Buffalo State University of New York  Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90579-4"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.12868"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000173836.09176.c4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa7322"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03780-1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002337"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001950"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201800186"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201302621"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.07.021"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063871"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-014-0133-y"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-016-0956-8"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2016.04.004"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2018.10.008"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2018.09.007"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2018.02.010"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008168"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1388"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ctg.2016.49"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32160-8"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21808"},{"key":"e_1_2_10_24_1","unstructured":"Food and Drug Administration Center for Biologics Evaluation and Research. 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