Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD.
BACKGROUND
The safety and efficacy of paricalcitol injection have been well established for the prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stage 5. The capsule form of paricalcitol was developed to provide a convenient dosage form for patients with stages 3 and 4 CKD.


METHODS
Three randomized, placebo-controlled, phase-3 trials were conducted in patients with stages 3 and 4 CKD with SHPT. Enrollment criteria included an estimated glomerular filtration rate between 15 and 60 mL/min/1.73 m2 (0.25 and 1.00 mL/s/1.73 m2), an average of 2 consecutive intact parathyroid hormone (iPTH) levels greater than 150 pg/mL (ng/L), 2 consecutive serum calcium levels between 8.0 and 10.0 mg/dL (2.00 and 2.50 mmol/L), and 2 consecutive serum phosphorus levels of 5.2 mg/dL or less (< or = 1.68 mmol/L). Two studies used a thrice-weekly dosing regimen and 1 study used a once-daily dosing regimen for 24 weeks. Dosing was based on serum iPTH, calcium, and phosphorus levels. The primary efficacy end point is 2 consecutive decreases in iPTH levels greater than 30% from baseline.


RESULTS
Two hundred twenty patients participated (n = 107, paricalcitol; n = 113, placebo). At least 2 consecutive decreases in iPTH levels of 30% or greater from baseline occurred in 91% of paricalcitol versus 13% of placebo patients (P < 0.001). Incidences of hypercalcemia, hyperphosphatemia, and elevated calcium-phosphorus product levels were not significantly different between groups. Similarly, no significant differences in urinary calcium and phosphorus excretion or deterioration in kidney function were detected in patients administered paricalcitol compared with placebo.


CONCLUSIONS
Paricalcitol capsule was well tolerated and effectively decreased iPTH levels with minimal or no impact on calcium levels, phosphorus balance, and kidney function in patients with stages 3 and 4 CKD.
Coyne
Daniel
D
Renal Division, Department of Internal Medicine, Chromalloy American Kidney Center, Washington University, St Louis, MO, USA.
Acharya
Muralidhar
M
Qiu
Ping
P
Abboud
Hanna
H
Batlle
Daniel
D
Rosansky
Steven
S
Fadem
Stephen
S
Levine
Barton
B
Williams
Laura
L
Andress
Dennis L
DL
Sprague
Stuart M
SM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002214:Capsules; D018450:Disease Progression; D004311:Double-Blind Method; D004872:Ergocalciferols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D002214:Capsules; D004872:Ergocalciferols; C084656:paricalcitol