Dose-response Study of Paricalcitol Injection in Chronic Kidney Disease Patients Receiving Hemodialysis

Late Phase 2 Study of Paricalcitol Injection: Dose-response Study of Paricalcitol Injection in Chronic Kidney Disease Subjects Receiving Hemodialysis With Secondary Hyperparathyroidism (Examination of Initial Dose and Incremental Dose)

The purpose of this study was to investigate the initial dose and dose adjustment range for paricalcitol injection in patients with chronic kidney disease on hemodialysis who have secondary hyperparathyroidism.

This multicenter, randomized, open-label trial consisted of 4 dose-adjustment regimens for paricalcitol injection (initial doses and dose adjustment ranges were 2 ± 1 µg, 2 ± 2 µg, 4 ± 1 µg, and 4 ± 2 µg) and 1 maxacalcitol regimen (initial dose and dose adjustment range was 5 µg ± 2.5 µg or 10 µg ± 2.5 µg) as a reference group. Subjects who met the inclusion criteria were randomized equally to 1 of the treatment groups with iPTH values at screening (< 500 pg/mL or ≥ 500 pg/mL) as a dynamic allocation factor. Study drugs were administered 3 times weekly (every other day) from the venous end of the hemodialysis circuit just before completion of the dialysis session. The initial doses were continued for 2 weeks, followed by dose adjustments (increase, maintenance, decrease, suspension, or resumption) by 1 µg or 2 µg units for the paricalcitol groups and by 2.5 µg units for the maxacalcitol group based on iPTH, calcium (adjusted), and phosphorus values every 2 weeks.

Subjects in the paricalcitol groups were to be suspended from treatment if their iPTH value decreased to < 60 pg/mL in accordance with the guidelines proposed by the Japanese Society of Dialysis Therapy for the treatment of secondary hyperparathyroidism in chronic dialysis patients (control goal value of 60-180 pg/mL for iPTH). The dose adjustment criteria based on iPTH values for the maxacalcitol group were set according to the prescribing information for maxacalcitol (suspended when iPTH decreased to ≤ 150 pg/mL).

Inclusion Criteria:

• Diagnosed with chronic kidney disease receiving hemodialysis 3 times a week for at least 3 months prior to obtaining the informed consent and scheduled to be receiving the same hemodialysis during the study period.
• Using dialysate with constant concentration of calcium for 4 weeks prior to obtaining informed consent and phosphate binder with constant dose regimen for 2 weeks prior to obtaining informed consent.
• Intact parathyroid hormone level (iPTH) ≥ 300 pg/mL
• Calcium (adjusted) 8.4-10.2 milligrams/deciliter (mg/dL)
• Phosphorus ≤ 6.5 mg/dL
• Age ≥ 20 years

Exclusion Criteria:

• History of allergic reaction or significant sensitivity to vitamin D or vitamin D related compounds
• Parathyroidectomy or ethanol infusion within past year
• Progressive malignancy or clinically significant hepatic diseases, severe cerebral/cardiovascular diseases, severe hypertension, or uncontrolled diabetes mellitus
• Drug or alcohol abuse within past 6 months
• Taking calcitonin, maintenance intravenous or oral glucocorticoids, cinacalcet, bisphosphonates, selective estrogen-receptor modulator (SERM), vitamin D compounds (other than study drug), or other drugs that may affect calcium or bone metabolism (other than estrogen or progestin, vitamin K2)
• Will need to take chronic dose (≥ 2 consecutive weeks) of cytochrome P450 (CYP3A) inhibitors (e.g., clarithromycin, grapefruit products) or inducers (e.g., carbamazepine, rifampicin)
• Taking aluminum containing products (2 weeks prior to consent)