Use of 2MD, a novel oral calcitriol analog, in hemodialysis patients with secondary hyperparathyroidism

Richa Pandey, Julia Zella, Margaret Clagett-Dame, Lori A. Plum, Hector F. DeLuca, Daniel W. Coyne

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: Use of existing therapies for secondary hyperparathyroidism (SHPT), such as calcitriol or paricalcitol, is frequently limited by the development of hypercalcemia. 2-Methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD; DP001) is a novel and a more potent vitamin D receptor activator (VDRA) that more selectively localizes in the parathyroid gland, and has a wider therapeutic margin in the uremic rat model than calcitriol and paricalcitol. Design, Setting, Participants, and Measurements: Hemodialysis patients were enrolled and dosed with 110, 220, 330, 440, or 550 ng of 2MD orally thrice weekly for 4 weeks. Responders were defined as patients having a ≥30% reduction in parathyroid hormone (PTH) from baseline, and were assessed at weeks 2 and 4. Results: Of 31 patients recruited, 24 completed the 4-week treatment. There was little or no reduction in PTH in the 110 and 220 ng dose cohorts. Higher dose cohorts had greater PTH suppression with more than half the patients in the 440 and 550 ng dose cohorts considered responders (≥30% PTH reduction from baseline). None had oversuppression of PTH or hypercalcemia (corrected serum calcium >10.6 mg/dl). Plasma drug concentration increased with increasing dose, and all responders achieved a 2MD concentration of ≥1.5 pg/ml. All dose levels of 2MD were well tolerated without safety concerns. Conclusions: In hemodialysis patients with SHPT, 2MD, at thrice weekly oral doses of 440 and 550 ng, is well tolerated and effectively suppresses PTH without hypercalcemia. Future studies are needed to study the long-term implications of treating ESRD patients with this novel VDRA.

Original languageEnglish
Pages (from-to)213-220
Number of pages8
JournalAmerican Journal of Nephrology
Volume43
Issue number3
DOIs
StatePublished - May 1 2016

Keywords

  • Calcitriol
  • Hemodialysis
  • Parathyroid hormone
  • Secondary hyperparathyroidism

Fingerprint

Dive into the research topics of 'Use of 2MD, a novel oral calcitriol analog, in hemodialysis patients with secondary hyperparathyroidism'. Together they form a unique fingerprint.

Cite this