{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:01:40Z","timestamp":1790280100758,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Lucerastat is an iminosugar with the potential to provide substrate reduction therapy for the treatment of Fabry disease (FD), an inherited X\u2010linked lysosomal storage disorder. The aims of this study were to develop a population pharmacokinetic (PK) model describing lucerastat plasma concentration over time, to investigate the relationships between subject\u2010specific characteristics and model parameters, and to assess the influence of these differences between subjects on lucerastat exposure via model\u2010based simulations. Longitudinal nonlinear mixed effects modeling was applied to develop a model based on data from 250 participants in six Phase\u00a01 and two Phase\u00a03 studies. Lucerastat pharmacokinetics were described by a two\u2010compartment model with linear first\u2010order absorption and elimination, including allometric scaling of body weight on clearance and volume parameters. Lucerastat clearance was reduced in subjects with lower estimated glomerular filtration rate (eGFR). Disease status (with\/without FD) was found to impact clearance and volumes of distribution to a limited extent. The model described the data well across the dose range from 100 to 4000 mg. Body weight, disease status, and renal function were shown to influence exposure, with dose adaptation only required in patients with renal function impairment, as body weight and disease status had limited impact. Dose adaptation as applied in Phase\u00a03 (i.e., eGFR [mL\/min\/1.73 m\n                    <jats:sup>2<\/jats:sup>\n                    ] \u226560: 1000\u00a0mg; \u226545 and &lt;60: 750\u00a0mg; \u226530 and &lt;45: 500\u00a0mg; \u226515 and &lt;30: 250\u00a0mg b.i.d.) resulted in achieving similar exposure in study participants with FD with different levels of renal function impairment.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70247","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:18:26Z","timestamp":1784542706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Population Pharmacokinetic Modeling for the Iminosugar Lucerastat Supports Dose Adaptation in Patients With Fabry Disease and Moderate to Severe Renal Function Impairment"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0813-4463","authenticated-orcid":false,"given":"Janneke M.","family":"Brussee","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4083-5817","authenticated-orcid":false,"given":"Jasper","family":"Dingemanse","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9213-7079","authenticated-orcid":false,"given":"Dominik","family":"Lott","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7777-5734","authenticated-orcid":false,"given":"Benjamin","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3675-5259","authenticated-orcid":false,"given":"Aline","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Clinical Science Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4686-976X","authenticated-orcid":false,"given":"Andreas","family":"Krause","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2022.100862"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp031"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X20666220601124117"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfab038"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2018.02.014"},{"key":"e_1_2_9_7_1","unstructured":"EMA.Replagal (Agalsidase Alfa): Summary of product characteristics. European Medicines Agency ed.;2022. Accessed July 10 2026.https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/replagal-epar-product-information_en.pdf"},{"key":"e_1_2_9_8_1","unstructured":"FDA.Fabrazyme (Agalsidase Beta): Highlights of prescribing information. United States Food and Drug Administration ed.;2021. Accessed July 10 2026.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/103979s5303lbl.pdf"},{"key":"e_1_2_9_9_1","unstructured":"FDA.Elfabrio (Pegunigalsidase Alfa): Highlights of prescribing information. United States Food and Drug Administration ed.;2023. Accessed July 10 2026.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761161s000lbl.pdf"},{"key":"e_1_2_9_10_1","unstructured":"FDA.Galafold (Migalastat): Highlights of prescribing information. European Medicines Agency ed.;2021. Accessed July 10 2026.https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/galafold-epar-product-information_en.pdf"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018030329"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01621-y"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014121226"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00384-6"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy248"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-68256-5"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.790"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0565-9"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01582-7"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.944"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-019-02808-9"},{"key":"e_1_2_9_22_1","unstructured":"Idorsia Pharmaceuticals Ltd.A study to evaluate the long\u2010term safety and tolerability of lucerastat in adult subjects with Fabry disease. NCT03737214. Accessed July 10 2026.https:\/\/clinicaltrials.gov\/study\/NCT03737214"},{"key":"e_1_2_9_23_1","unstructured":"Idorsia Pharmaceuticals Ltd.Efficacy and safety of lucerastat oral monotherapy in adult subjects with Fabry disease (MODIFY). NCT03425539. Accessed July 10 2026.https:\/\/clinicaltrials.gov\/study\/NCT03425539"},{"key":"e_1_2_9_24_1","unstructured":"Idorsia Pharmaceuticals Ltd.An open\u2010label phase 3 study of lucerastat in Japanese subjects with Fabry disease. jRCT2080224659. Accessed July 10 2026.https:\/\/jrct.mhlw.go.jp\/en-latest-detail\/jRCT2080224659"},{"key":"e_1_2_9_25_1","unstructured":"Idorsia Pharmaceuticals Ltd.A multicenter open\u2010label long\u2010term continuous administration study to investigate the safety and tolerability of lucerastat in Japanese Fabry disease patients. jRCT2080224890. 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