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

Phase 2

Completed

• Conditions: Chronic Kidney Disease on Hemodialysis; Secondary Hyperparathyroidism
• Interventions: Drug: Paricalcitol; Drug: Maxacalcitol

• Registration Number: NCT00667576
• Lead Sponsor: Abbott

Brief Summary

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.

Detailed Description

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).

Study Timeline

• Study Start: 2008-04
• Study First Submitted: 2008-04-24
• Study First Submitted QC: 2008-04-25
• Study First Posted: 2008-04-28
• Primary Completion: 2009-03
• Study Completion: 2009-03
• Results First Submitted: 2010-03-18
• Results First Submitted QC: 2010-03-18
• Results First Posted: 2010-04-02
• Status Verified: 2012-01
• Last Update Submitted: 2012-01-18
• Last Update Posted: 2012-01-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 153

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Paricalcitol 2 µg ± 1 µg	Paricalcitol	Paricalcitol initial dosage 2 micrograms (µg) with incremental adjustment of 1 µg
Maxacalcitol 5 or 10 µg ± 2.5 µg	Maxacalcitol	Maxacalcitol initial dosage 5 or 10 µg with incremental adjustment of 2.5 µg
Paricalcitol 2 µg ± 2 µg	Paricalcitol	Paricalcitol initial dosage 2 µg with incremental adjustment of 2 µg
Paricalcitol 4 µg ± 1 µg	Paricalcitol	Paricalcitol initial dosage 4 µg with incremental adjustment of 1 µg
Paricalcitol 4 µg ± 2 µg	Paricalcitol	Paricalcitol initial dosage 4 µg with incremental adjustment of 2 µg

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects With ≥ 50% Decrease From Baseline in Intact Parathyroid Hormone (iPTH) Serum Level	Baseline to Week 13 (Final Visit)

Secondary Outcome Measures

Name	Time	Method
Duration of 2 Consecutive Decreases of ≥ 50% From Baseline in Intact Parathyroid Hormone (iPTH) Values	Through Week 13
Percentage of Subjects With 2 or More Decreases of ≥ 50% From Baseline in Intact Parathyroid Hormone (iPTH) Level	Through Week 13
Duration of 2 Consecutive Intact Parathyroid Hormone (iPTH) Values ≤ 180 pg/mL	Through Week 13
Percentage of Subjects With Intact Parathyroid Hormone (iPTH) ≤ 180 Picograms/Milliliter (pg/mL)	Baseline to Week 13 (Final Visit)
Mean Change From Baseline in Intact Parathyroid Hormone (iPTH) Level	Baseline to Week 13 (Final Visit)