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Effects of parathyroid hormone rhPTH(1-84) on phosphate homeostasis and vitamin D metabolism in hypoparathyroidism: REPLACE phase 3 study.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, E18-A, 200 1st Street SW, Rochester, MN, 55905, USA. clarke.bart@mayo.edu. Section of Endocrinology, University of Chicago Medicine, 5841 South Maryland Avenue, MC1027, Chicago, IL, 60637, USA. Division of Endocrinology, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, Room 864, New York, NY, 10032, USA. Endocrine Research Unit, San Francisco Department of Veterans Affairs Medical Center, University of California, 1700 Owens Street, San Francisco, CA, 94158, USA. NPS Pharmaceuticals, Inc., 300 Shire Way, Lexington, MA, 02421, USA. Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, 50 Blossom Street, Thier-1123, Boston, MA, 02114, USA.

Endocrine. 2017;(1):273-282
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Abstract

In hypoparathyroidism, inappropriately low levels of parathyroid hormone lead to unbalanced mineral homeostasis. The objective of this study was to determine the effect of recombinant human parathyroid hormone, rhPTH(1-84), on phosphate and vitamin D metabolite levels in patients with hypoparathyroidism. Following pretreatment optimization of calcium and vitamin D doses, 124 patients in a phase III, 24-week, randomized, double-blind, placebo-controlled study of adults with hypoparathyroidism received subcutaneous injections of placebo or rhPTH(1-84) (50 µg/day, titrated to 75 and then 100 µg/day, to permit reductions in oral calcium and active vitamin D doses while maintaining serum calcium within 2.0-2.2 mmol/L). Predefined endpoints related to phosphate homeostasis and vitamin D metabolism were analyzed. Serum phosphate levels decreased rapidly from the upper normal range and remained lower with rhPTH(1-84) (P < 0.001 vs. placebo). At week 24, serum calcium-phosphate product was lower with rhPTH(1-84) vs. placebo (P < 0.001). rhPTH(1-84) treatment resulted in significant reductions in oral calcium dose compared with placebo (P < 0.001) while maintaining serum calcium. After pretreatment optimization, baseline serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) levels were within the normal range in both groups. After 24 weeks, 1,25(OH)2D levels were unchanged in both treatment groups, despite significantly greater reductions in active vitamin D dose in the rhPTH(1-84) group. In hypoparathyroidism, rhPTH(1-84) reduces serum phosphate levels, improves calcium-phosphate product, and maintains 1,25(OH)2D and serum calcium in the normal range while allowing significant reductions in active vitamin D and oral calcium doses.

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