{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T19:59:24Z","timestamp":1774641564853,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007723","name":"Takeda Pharmaceuticals U.S.A.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007723","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Recombinant human parathyroid hormone (1\u201084), rhPTH(1\u201084), is an approved adjunctive treatment to oral calcium and active vitamin D for adult patients with hypoparathyroidism; however, there is limited information on the effect of twice daily (BID) dosing of rhPTH(1\u201084). This was a phase I, open\u2010label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism. The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1\u201084) administered subcutaneously at 25\u2009\u03bcg BID, 50\u2009\u03bcg BID, and 100\u2009\u03bcg once daily (QD) with or without supplemental oral calcium. Safety and tolerability were evaluated as secondary objectives. In total, 33 patients with chronic hypoparathyroidism completed the study. Treatment with rhPTH(1\u201084), both BID and QD, over the short\u2010term maintained serum calcium, lowered serum phosphorus, decreased urinary calcium excretion, and increased urinary phosphorus excretion. The decrease in urinary calcium excretion was numerically greater for BID than QD. Generally, baseline\u2010adjusted pharmacokinetic parameters including area under the curve and maximum observed concentration increased with increasing rhPTH(1\u201084) dose, although this effect was not dose proportional. No new safety findings were observed. Our study revealed no differences thought to be clinically meaningful in pharmacokinetic or pharmacodynamic parameters with BID versus QD rhPTH(1\u201084) dosing. Future long\u2010term studies are warranted to further elucidate the effects of alternative dosing strategies. \u00a9 2023 Takeda Development Center Americas, Inc and The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10758","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T02:41:26Z","timestamp":1685587286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Phase I Randomized Trial of Once\u2010Daily Versus\n                    <scp>Twice\u2010Daily<\/scp>\n                    Recombinant Human Parathyroid Hormone (1\u201084) for Hypoparathyroidism"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4343-6723","authenticated-orcid":false,"given":"Steven W.","family":"Ing","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism Ohio State University Wexner Medical Center  Columbus OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard D.","family":"Finkelman","sequence":"additional","affiliation":[{"name":"Takeda Pharmaceuticals USA, Inc.  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