Affiliation:
1. Division of Endocrinology, Diabetes, and Metabolism Ohio State University Wexner Medical Center Columbus OH USA
2. Takeda Pharmaceuticals USA, Inc. Lexington MA USA
3. Divisions of Endocrinology and Metabolism and Geriatrics McMaster University Oakville ON Canada
4. Endocrine Unit Massachusetts General Hospital and Harvard Medical School Boston MA USA
5. Department of Clinical Medicine – Department of Endocrinology and Internal Medicine Aarhus University and Aarhus University Hospital Aarhus Denmark
6. Department of Internal Medicine and Oncology Semmelweis University Budapest Hungary
Abstract
ABSTRACTRecombinant human parathyroid hormone (1‐84), rhPTH(1‐84), 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(1‐84). This was a phase I, open‐label, 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(1‐84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg 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(1‐84), both BID and QD, over the short‐term 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‐adjusted pharmacokinetic parameters including area under the curve and maximum observed concentration increased with increasing rhPTH(1‐84) 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(1‐84) dosing. Future long‐term studies are warranted to further elucidate the effects of alternative dosing strategies. © 2023 Takeda Development Center Americas, Inc and The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Funder
Takeda Pharmaceuticals U.S.A.
Publisher
Oxford University Press (OUP)
Subject
Orthopedics and Sports Medicine,Endocrinology, Diabetes and Metabolism
Cited by
1 articles.
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