Safety and Efficacy of Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism Randomly Assigned to Receive Fixed 25-μg or 50-μg Daily Doses

John P. Bilezikian, Bart Clarke, Michael Mannstadt, Jeffrey Rothman, Tamara Vokes, Hak Myung Lee, Alan Krasner

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose The present study examined the efficacy and safety of a lower rhPTH(1–84) dose. Methods RELAY was a dose-blinded, multicenter, 8-week study of patients with hypoparathyroidism randomized to fixed 25- or 50-μg/d doses of subcutaneous rhPTH(1–84). The primary end point was the percentage of patients at week 8 with supplement reductions in calcium to ≤500 mg/d and in calcitriol to ≤0.25 μg/d, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal. The secondary end point was the percentage of patients at week 8 with a ≥50% reduction in calcium and calcitriol doses, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal. Findings Forty-two patients were randomized (25-μg group, n = 19; 50-μg group, n = 23). At week 8, the primary end point was achieved by 4 (21%; 95% CI, 6%–46%) and 6 (26%; 95% CI, 10%–48%) of the patients receiving 25 and 50 μg/d of rhPTH(1–84), respectively. The secondary end point was achieved by 2 (11%; 95% CI, 1%–33%) and 6 (26%; 95% CI, 10%–48%) of the patients receiving 25 and 50 μg/d of rhPTH(1–84), respectively. Treatment-emergent adverse events were reported by 11 (58%) patients in the 25-μg group and 17 (74%) patients in the 50-μg group. Implications Doses as low as 25 µg/d of rhPTH(1–84) are well tolerated and may be effective for a subset of patients. ClinicalTrials.gov identifier: NCT01268098.

Original languageEnglish (US)
Pages (from-to)2096-2102
Number of pages7
JournalClinical Therapeutics
Volume39
Issue number10
DOIs
StatePublished - Oct 1 2017

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Hypoparathyroidism
Safety
Calcium
Calcitriol
human PTH protein
Serum

Keywords

  • calcium
  • clinical trial
  • hypoparathyroidism
  • recombinant human parathyroid hormone
  • vitamin D

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Safety and Efficacy of Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism Randomly Assigned to Receive Fixed 25-μg or 50-μg Daily Doses. / Bilezikian, John P.; Clarke, Bart; Mannstadt, Michael; Rothman, Jeffrey; Vokes, Tamara; Lee, Hak Myung; Krasner, Alan.

In: Clinical Therapeutics, Vol. 39, No. 10, 01.10.2017, p. 2096-2102.

Research output: Contribution to journalArticle

Bilezikian, John P. ; Clarke, Bart ; Mannstadt, Michael ; Rothman, Jeffrey ; Vokes, Tamara ; Lee, Hak Myung ; Krasner, Alan. / Safety and Efficacy of Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism Randomly Assigned to Receive Fixed 25-μg or 50-μg Daily Doses. In: Clinical Therapeutics. 2017 ; Vol. 39, No. 10. pp. 2096-2102.
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AU - Clarke, Bart

AU - Mannstadt, Michael

AU - Rothman, Jeffrey

AU - Vokes, Tamara

AU - Lee, Hak Myung

AU - Krasner, Alan

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AB - Purpose The present study examined the efficacy and safety of a lower rhPTH(1–84) dose. Methods RELAY was a dose-blinded, multicenter, 8-week study of patients with hypoparathyroidism randomized to fixed 25- or 50-μg/d doses of subcutaneous rhPTH(1–84). The primary end point was the percentage of patients at week 8 with supplement reductions in calcium to ≤500 mg/d and in calcitriol to ≤0.25 μg/d, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal. The secondary end point was the percentage of patients at week 8 with a ≥50% reduction in calcium and calcitriol doses, while maintaining serum calcium levels between 1.875 mmol/L and the upper limit of normal. Findings Forty-two patients were randomized (25-μg group, n = 19; 50-μg group, n = 23). At week 8, the primary end point was achieved by 4 (21%; 95% CI, 6%–46%) and 6 (26%; 95% CI, 10%–48%) of the patients receiving 25 and 50 μg/d of rhPTH(1–84), respectively. The secondary end point was achieved by 2 (11%; 95% CI, 1%–33%) and 6 (26%; 95% CI, 10%–48%) of the patients receiving 25 and 50 μg/d of rhPTH(1–84), respectively. Treatment-emergent adverse events were reported by 11 (58%) patients in the 25-μg group and 17 (74%) patients in the 50-μg group. Implications Doses as low as 25 µg/d of rhPTH(1–84) are well tolerated and may be effective for a subset of patients. ClinicalTrials.gov identifier: NCT01268098.

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