{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:10:25Z","timestamp":1792059025551,"version":"4.4.0"},"reference-count":20,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100006259","name":"Teva Pharmaceutical Industries","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006259","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Potential fremanezumab doses for pediatric patients were evaluated using pharmacokinetic modeling and simulation. An open-label phase 1 pharmacokinetic and safety study was conducted in pediatric patients with migraine. This study\u2019s results together with refinement of the adult population pharmacokinetic model were used to determine fremanezumab dose recommendations for phase 3 pediatric studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Initial application of the adult model suggested that a 75 mg dose in pediatric patients would match exposures determined safe and efficacious in adults; thus, in the phase 1 study, 15 patients, aged 6\u201311 years and weighing 17\u201345\u2009kg received a single subcutaneous 75 mg fremanezumab dose. The sparse pharmacokinetic data collected were used to refine the adult model and simulate concentration-time profiles for monthly subcutaneous doses (60 to 225 mg) in a virtual pediatric population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the phase 1 pediatric study, the safety profile was similar to that of adults. A two-compartment model with first-order absorption and elimination and body weight effects on clearance and central volume was found to adequately describe the pediatric pharmacokinetic data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Using exposure matching to the effective adult fremanezumab dose (225 mg subcutaneous monthly), modeling and simulations predict recommended dose of 120 mg in pediatric patients weighing\u2009&lt;\u200945\u2009kg. Registration: The phase 1 study of this report is registered at EudraCT with the identifier 2018-000734-35.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024211007789","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T02:25:05Z","timestamp":1621304705000},"page":"1065-1074","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Dose selection for fremanezumab (AJOVY) phase 3 pediatric migraine studies using pharmacokinetic data from a pediatric phase 1 study and a population pharmacokinetic modeling and simulation approach"],"prefix":"10.1177","volume":"41","author":[{"given":"Orit","family":"Cohen-Barak","sequence":"first","affiliation":[{"name":"Teva Pharmaceutical Industries, Netanya, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrijana","family":"Radivojevic","sequence":"additional","affiliation":[{"name":"IntiGrowth LLC, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aksana","family":"Jones","sequence":"additional","affiliation":[{"name":"Cognigen Corporation, a Simulations Plus company, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Fiedler-Kelly","sequence":"additional","affiliation":[{"name":"Cognigen Corporation, a Simulations Plus company, Buffalo, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gillespie","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries, West Chester, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brennan","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries, West Chester, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dikla","family":"Gutman","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries, Netanya, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Rasamoelisolo","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries, West Chester, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Hallak","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries, Netanya, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pippa","family":"Loupe","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries, West Chester, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoel","family":"Kessler","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries, Netanya, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Ning","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries, West Chester, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha","family":"Levi","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries, West Chester, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H","family":"Ahn","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries, West Chester, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rabinovich-Guilatt","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries, Netanya, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"bibr1-03331024211007789","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709038"},{"key":"bibr2-03331024211007789","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.4853"},{"key":"bibr3-03331024211007789","doi-asserted-by":"publisher","DOI":"10.1111\/head.13845"},{"key":"bibr4-03331024211007789","doi-asserted-by":"publisher","DOI":"10.1111\/head.12505_2"},{"key":"bibr5-03331024211007789","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-015-0125-5"},{"key":"bibr6-03331024211007789","unstructured":"Topiramate, Janssen Pharmaceuticals, Inc., Titusville, NJ, USA (package insert). https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/020505s057_020844s048lbl.pdf. (2017, accessed 14 January 2021)."},{"key":"bibr7-03331024211007789","first-page":"529","volume":"63","author":"Sakulchit T","year":"2017","journal-title":"Can Fam Physician"},{"key":"bibr8-03331024211007789","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-3487"},{"key":"bibr9-03331024211007789","unstructured":"US Food and Drug Administration. General clinical pharmacology considerations for pediatric studies for drugs and biological products \u2013 guidance for industry, 2014 https:\/\/www.fda.gov\/downloads\/drugs\/guidances\/ucm425885.pdf (accessed 15 January 2021)."},{"key":"bibr10-03331024211007789","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-020-00382-7"},{"key":"bibr11-03331024211007789","author":"Cherniakov I","journal-title":". 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Clinical growth charts, https:\/\/www.cdc.gov\/growthcharts\/clinical_charts.html (2000, accessed 15 January 2021)."},{"key":"bibr16-03331024211007789","doi-asserted-by":"publisher","DOI":"10.1177\/0333102418771376"},{"key":"bibr17-03331024211007789","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-015-1973-1"},{"key":"bibr18-03331024211007789","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2013.465"},{"key":"bibr19-03331024211007789","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1434"},{"key":"bibr20-03331024211007789","unstructured":"US Food and Drug Administration. 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