{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T21:23:02Z","timestamp":1768598582173,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nintedanib reduces the rate of decline in forced vital capacity (FVC) in adult patients with idiopathic pulmonary fibrosis (IPF), chronic progressive\u2010fibrosing interstitial lung diseases (ILDs) and systemic sclerosis\u2010associated ILD (SSc\u2010ILD). A pediatric Phase 3 trial (InPedILD) has been conducted in children 6\u201317\u2009years, and partial extrapolation from adults to pediatrics was performed to support dose selection and benefit\u2013risk assessment in pediatric patients with progressive\u2010fibrosing ILDs. Previously developed population pharmacokinetic (popPK) and efficacy exposure\u2010response (ER) meta\u2010models across all non\u2010oncologic pulmonary indications of nintedanib in adults were used as a basis for partial extrapolation to pediatric patients. Data from InPedILD and its open\u2010label extension trial (InPedILD\u2010ON) were incorporated and a Bayesian approach was utilized to extrapolate PK and FVC\u2010based efficacy endpoints. PK of nintedanib was adequately described using a similar structure as the adult popPK model. The weight\u2010based dosing scheme applied in InPedILD resulted in exposures similar to those in adult patients receiving the approved dose of nintedanib 150\u2009mg twice daily. The ER models for FVC %predicted and FVC\n                    <jats:italic>Z<\/jats:italic>\n                    \u2010score were similar to those developed in adults. Compared to adults, pediatric patients showed a slower estimated rate of decline for both endpoints. The estimated EC50 and Emax values in children and adolescents were comparable to those in adults. Partial extrapolation from adult to pediatric patients showed that the pre\u2010defined pediatric dosing regimen resulted in similar nintedanib exposures compared to the efficacious exposures in adults. ER models suggested a similar beneficial treatment effect of nintedanib on FVC in children and adults.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70135","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T17:41:32Z","timestamp":1765302092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics and Exposure\u2010Response Model\u2010Based Bayesian Extrapolation of\n                    <scp>FVC<\/scp>\n                    \u2010Based Efficacy Endpoints From Adults to Pediatric Patients Receiving Nintedanib"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0693-0562","authenticated-orcid":false,"given":"Sonja","family":"Hartmann","sequence":"first","affiliation":[{"name":"Translational Medicine and Clinical Pharmacology Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1524-7490","authenticated-orcid":false,"given":"Anna","family":"Chan Kwong","sequence":"additional","affiliation":[{"name":"Pharmetheus AB  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3572-9711","authenticated-orcid":false,"given":"Jakob","family":"Ribbing","sequence":"additional","affiliation":[{"name":"Pharmetheus AB  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Gahlemann","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim (Schweiz) GmbH  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3807-3323","authenticated-orcid":false,"given":"Julia","family":"Korell","sequence":"additional","affiliation":[{"name":"Translational Medicine and Clinical Pharmacology Boehringer Ingelheim Pharmaceuticals, Inc.  Ridgefield Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"European Medicines Agency \u201cOfev (European Public Assessment Report) \u201d2020 https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/ofev."},{"key":"e_1_2_9_3_1","unstructured":"U.S. Food & Drug Administration \u201cOFEV (nintedanib): Prescribing Information \u201d2020 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/205832s013lbl.pdf."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402584"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103690"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2016-209701"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903076"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908681"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00080312"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00805-2020"},{"key":"e_1_2_9_11_1","unstructured":"R.Deterding L.Young E.Deboer et\u00a0al. \u201cNintedanib in Children and Adolescents With Fibrosing ILDs: Interim Analysis of InPedlLD\u2010ON \u201d34th Int Cong of the European Respiratory Society (ERS) Vienna 7\/Sep\/2024\u201311\/Sep\/2024; 2024; Abstr."},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022972420004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-020-09695-z"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011970125687"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12838"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-024-09911-0"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1025"},{"key":"e_1_2_9_18_1","unstructured":"M. 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