A comparison of dosing regimens of paricalcitol capsule for the treatment of secondary hyperparathyroidism in CKD stages 3 and 4.
BACKGROUND
Intermittent dosing of calcitriol for secondary hyperparathyroidism (SHPT) has been associated with greater parathyroid hormone (PTH) reduction with fewer calcemic and phosphatemic effects than daily (QD) dosing.


METHODS
Secondary analyses of three randomized, double-blind, placebo-controlled multicenter studies in stage 3 and 4 chronic kidney disease (CKD) patients with SHPT were performed to compare three times per week (TIW) with QD dosing of paricalcitol. The pharmacokinetics of TIW and QD dosing of paricalcitol capsules were assessed in a separate group of healthy subjects.


RESULTS
Pharmacokinetics revealed similar steady state paricalcitol exposure between dosing regimens. In CKD patients, baseline data were similar between the TIW studies (n = 72, paricalcitol; n = 73, placebo) and QD studies (n = 35, paricalcitol; n = 40, placebo). Both dosing regimens resulted in similar efficacy (91%) for the primary end point of two consecutive > or = 30% decreases in intact PTH from baseline, but the QD regimen resulted in a greater percent reduction in intact PTH from baseline. The chances for developing increased serum calcium and phosphorus levels or Ca x P product were similar between paricalcitol and placebo groups for both treatment regimens. Furthermore, no difference in the risk for these elevations was detected between the TIW and QD regimens.


CONCLUSIONS
QD dosing of paricalcitol capsules is as efficacious as TIW dosing in achieving the primary end point (2 consecutive > or = 30% reductions in PTH) in stage 3 and 4 CKD patients with SHPT. Moreover, the QD regimen had no significant effect on hypercalcemia, hyperphosphatemia or Ca x P product as compared with placebo or intermittent dosing.
University of Texas Health Science Center, San Antonio, Texas, USA.
Hanna
H
Abboud
Daniel
D
Coyne
Olgierd
O
Smolenski
Michael
M
Anger
Norman
N
Lunde
Ping
P
Qiu
Rich
R
Hippensteel
Rajendra S
RS
Pradhan
Rameshraja V
RV
Palaparthy
Anne
A
Kavanaugh
Joel Z
JZ
Melnick
Laura A
LA
Williams
Daniel
D
Batlle
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000097:blood; D002214:Capsules; D002908:Chronic Disease; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004872:Ergocalciferols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy*; D007674:Kidney Diseases / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011446:Prospective Studies; D014815:Vitamins / Q000008:administration & dosage / Q000493:pharmacokinetics
D002214:Capsules; D004872:Ergocalciferols; D010281:Parathyroid Hormone; D014815:Vitamins; D010758:Phosphorus; C084656:paricalcitol; D002118:Calcium