title: Modified-release calcifediol effectively controls secondary hyperparathyroidism associated with vitamin D insufficiency in chronic kidney disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Oral MR calcifediol appears safe and highly effective in treating SHPT associated with vitamin D insufficiency in CKD.
authors.affiliation: NorthShore University Health System-University of Chicago, Pritzker School of Medicine, Evanston, Ill., USA.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Sprague
authors.forename: Arnold L
authors.initials: AL
authors.lastname: Silva
authors.forename: Fahd
authors.initials: F
authors.lastname: Al-Saghir
authors.forename: Radhika
authors.initials: R
authors.lastname: Damle
authors.forename: Samir P
authors.initials: SP
authors.lastname: Tabash
authors.forename: Martin
authors.initials: M
authors.lastname: Petkovich
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Messner
authors.forename: Jay A
authors.initials: JA
authors.lastname: White
authors.forename: Joel Z
authors.initials: JZ
authors.lastname: Melnick
authors.forename: Charles W
authors.initials: CW
authors.lastname: Bishop
mesh_terms: D000328:Adult; D000368:Aged; D002112:Calcifediol / Q000008:administration & dosage* / Q000097:blood; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D014815:Vitamins / Q000008:administration & dosage* / Q000097:blood
chemical_list: D003692:Delayed-Action Preparations; D010281:Parathyroid Hormone; D014815:Vitamins; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002112:Calcifediol