Modified-Release Calcifediol Effectively Controls Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease

• Published in: American journal of nephrology Vol. 40; no. 6; pp. 535 - 545
• Main Authors: Sprague, Stuart M., Silva, Arnold L., Al-Saghir, Fahd, Damle, Radhika, Tabash, Samir P., Petkovich, Martin, Messner, Eric J., White, Jay A., Melnick, Joel Z., Bishop, Charles W.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.02.2015
• Subjects: Adult; Aged; Alfacalcidol; Calcifediol; Calcifediol - administration & dosage; Calcifediol - blood; Care and treatment; Complications and side effects; Controlled release technology; Delayed-Action Preparations; Development and progression; Double-Blind Method; Female; Health aspects; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary - blood; Hyperparathyroidism, Secondary - drug therapy; Hyperparathyroidism, Secondary - etiology; Kidney diseases; Male; Middle Aged; Original Report: Patient-Oriented, Translational Research; Parathyroid Hormone - blood; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - complications; Testing; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - blood; Vitamin D Deficiency - blood; Vitamin D Deficiency - drug therapy; Vitamin D Deficiency - etiology; Vitamins - administration & dosage; Vitamins - blood; United States; Calcitriol (1,25-dihydroxyvitamin D3); Parathyroid hormone (PTH); Calcifediol (25-hydroxyvitamin D3); Vitamin D; Secondary hyperparathyroidism (SHPT); Vitamin D insufficiency; Chronic kidney disease (CKD)
• ISSN: 0250-8095; 1421-9670; 1421-9670
• DOI: 10.1159/000369939

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.