Modified-release calcifediol effectively controls secondary hyperparathyroidism associated with vitamin D insufficiency in chronic kidney disease.

Abstract

BACKGROUND/AIMS:

Vitamin D insufficiency drives secondary hyperparathyroidism (SHPT) and is associated with increased cardiovascular mortality in patients with chronic kidney disease (CKD). SHPT is poorly addressed by current vitamin D repletion options. The present study evaluated a novel investigational vitamin D repletion therapy: a modified-release (MR) formulation of calcifediol designed to raise serum 25-hydroxyvitamin D in a gradual manner to minimize the induction of CYP24 and, thereby, improve the SHPT control.

METHODS:

This randomized, double-blind, placebo-controlled trial evaluated MR calcifediol in CKD subjects (n = 78) with plasma intact parathyroid hormone (iPTH) >70 pg/ml and serum total 25-hydroxyvitamin D <30 ng/ml. Subjects received daily treatment for six weeks with oral MR calcifediol (30, 60 or 90 µg) or a placebo.

RESULTS:

More than 90% of subjects treated with MR calcifediol achieved serum 25-hydroxyvitamin D levels ≥30 ng/ml versus 3% of subjects treated with placebo (p < 0.0001). Mean plasma iPTH decreased from baseline (140.3 pg/ml) by 20.9 ± 6.2% (SE), 32.8 ± 5.7 and 39.3 ± 4.3% in the 30, 60 and 90 µg dose groups, respectively, and increased 17.2 ± 7.8% in the pooled placebo group (p < 0.005). No clinically significant safety concerns arose during MR calcifediol treatment.

CONCLUSION:

Oral MR calcifediol appears safe and highly effective in treating SHPT associated with vitamin D insufficiency in CKD.

• Authors: Stuart M Sprague, Arnold L Silva, Fahd Al-Saghir, Radhika Damle, Samir P Tabash, Martin Petkovich, Eric J Messner, Jay A White, Joel Z Melnick, Charles W Bishop
• Journal: American journal of nephrology (Am J Nephrol) Vol. 40 Issue 6 Pg. 535-45 ( 2014) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 25572630 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Delayed-Action Preparations
• Parathyroid Hormone
• Vitamins
• Vitamin D
• 25-hydroxyvitamin D
• Calcifediol

Topics

• Adult
• Aged
• Calcifediol (administration & dosage, blood)
• Delayed-Action Preparations
• Double-Blind Method
• Female
• Humans
• Hyperparathyroidism, Secondary (blood, drug therapy, etiology)
• Male
• Middle Aged
• Parathyroid Hormone (blood)
• Renal Insufficiency, Chronic (blood, complications)
• Vitamin D (analogs & derivatives, blood)
• Vitamin D Deficiency (blood, drug therapy, etiology)
• Vitamins (administration & dosage, blood)