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Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease.
Am J Nephrol. 2016; 44(4):316-325.AJ

Abstract

BACKGROUND/AIMS

Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23.

METHODS

Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks.

RESULTS

ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events.

CONCLUSION

Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD.

Authors+Show Affiliations

NorthShore University Health System-University of Chicago, Pritzker School of Medicine, Evanston, Ill., USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

27676085

Citation

Sprague, Stuart M., et al. "Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease." American Journal of Nephrology, vol. 44, no. 4, 2016, pp. 316-325.
Sprague SM, Crawford PW, Melnick JZ, et al. Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease. Am J Nephrol. 2016;44(4):316-325.
Sprague, S. M., Crawford, P. W., Melnick, J. Z., Strugnell, S. A., Ali, S., Mangoo-Karim, R., Lee, S., Petkovich, P. M., & Bishop, C. W. (2016). Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease. American Journal of Nephrology, 44(4), 316-325.
Sprague SM, et al. Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease. Am J Nephrol. 2016;44(4):316-325. PubMed PMID: 27676085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease. AU - Sprague,Stuart M, AU - Crawford,Paul W, AU - Melnick,Joel Z, AU - Strugnell,Stephen A, AU - Ali,Shaukat, AU - Mangoo-Karim,Roberto, AU - Lee,Sungchun, AU - Petkovich,P Martin, AU - Bishop,Charles W, Y1 - 2016/09/28/ PY - 2016/08/15/received PY - 2016/09/10/accepted PY - 2016/10/19/pubmed PY - 2018/1/10/medline PY - 2016/9/28/entrez SP - 316 EP - 325 JF - American journal of nephrology JO - Am J Nephrol VL - 44 IS - 4 N2 - BACKGROUND/AIMS: Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. METHODS: Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks. RESULTS: ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events. CONCLUSION: Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD. SN - 1421-9670 UR - https://www.unboundmedicine.com/medline/citation/27676085/Use_of_Extended_Release_Calcifediol_to_Treat_Secondary_Hyperparathyroidism_in_Stages_3_and_4_Chronic_Kidney_Disease_ L2 - https://www.karger.com?DOI=10.1159/000450766 DB - PRIME DP - Unbound Medicine ER -