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.

Study Overview

• Status: Completed
• Conditions: Secondary Hyperparathyroidism; Chronic Kidney Disease on Hemodialysis
• Intervention / Treatment: Drug: Paricalcitol; Drug: Maxacalcitol

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 Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Metropolis
    • Tokyo, Metropolis, Japan
  • Prefecture
    • Aichi, Prefecture, Japan
    • Chiba, Prefecture, Japan
    • Fukuoka, Prefecture, Japan
    • Hokkaido, Prefecture, Japan
    • Ibaragi, Prefecture, Japan
    • Kanagawa, Prefecture, Japan
    • Kumamoto, Prefecture, Japan
    • Nagano, Prefecture, Japan
    • Nagasaki, Prefecture, Japan
    • Osaka, Prefecture, Japan
    • Saitama, Prefecture, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Paricalcitol 2 µg ± 1 µg; Paricalcitol initial dosage 2 micrograms (µg) with incremental adjustment of 1 µg	Drug: Paricalcitol; Study drug was administered 3 times per week (no more frequently than every other day) intravenously immediately before the completion of hemodialysis. The initial dosage was administered for 2 weeks, with subsequent dosage adjustment based on the subject's iPTH, calcium (adjusted), and phosphorus levels every 2 weeks. Total duration of treatment was 12 weeks.; Other Names: Zemplar; ABT-358
EXPERIMENTAL: Paricalcitol 2 µg ± 2 µg; Paricalcitol initial dosage 2 µg with incremental adjustment of 2 µg	Drug: Paricalcitol; Study drug was administered 3 times per week (no more frequently than every other day) intravenously immediately before the completion of hemodialysis. The initial dosage was administered for 2 weeks, with subsequent dosage adjustment based on the subject's iPTH, calcium (adjusted), and phosphorus levels every 2 weeks. Total duration of treatment was 12 weeks.; Other Names: Zemplar; ABT-358
EXPERIMENTAL: Paricalcitol 4 µg ± 1 µg; Paricalcitol initial dosage 4 µg with incremental adjustment of 1 µg	Drug: Paricalcitol; Study drug was administered 3 times per week (no more frequently than every other day) intravenously immediately before the completion of hemodialysis. The initial dosage was administered for 2 weeks, with subsequent dosage adjustment based on the subject's iPTH, calcium (adjusted), and phosphorus levels every 2 weeks. Total duration of treatment was 12 weeks.; Other Names: Zemplar; ABT-358
EXPERIMENTAL: Paricalcitol 4 µg ± 2 µg; Paricalcitol initial dosage 4 µg with incremental adjustment of 2 µg	Drug: Paricalcitol; Study drug was administered 3 times per week (no more frequently than every other day) intravenously immediately before the completion of hemodialysis. The initial dosage was administered for 2 weeks, with subsequent dosage adjustment based on the subject's iPTH, calcium (adjusted), and phosphorus levels every 2 weeks. Total duration of treatment was 12 weeks.; Other Names: Zemplar; ABT-358
OTHER: Maxacalcitol 5 or 10 µg ± 2.5 µg; Maxacalcitol initial dosage 5 or 10 µg with incremental adjustment of 2.5 µg	Drug: Maxacalcitol; Study drug was administered 3 times per week (no more frequently than every other day) intravenously immediately before the completion of hemodialysis. The initial dosage was administered for 2 weeks, with subsequent dosage adjustment based on the subject's iPTH, calcium (adjusted), and phosphorus levels every 2 weeks. Total duration of treatment was 12 weeks.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Hypercalcemia	Hypercalcemia was defined as at least 1 adjusted calcium value > 11.5 mg/dL or at least 2 consecutive adjusted calcium values ≥ 11.0 mg/dL	Through Week 13
Percentage of Subjects With Hyperphosphatemia	Hyperphosphatemia was defined as at least 2 consecutive phosphorus values ≥ 7.0 mg/dL	Through Week 13

Collaborators and Investigators

• Sponsor: Abbott
• Collaborators: Abbott Japan Co.,Ltd
• Investigators: Study Director: Ryotaro Matsuzawa, Abbott

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (ACTUAL): March 1, 2009
• Study Completion (ACTUAL): March 1, 2009

Study Registration Dates

• First Submitted: April 24, 2008
• First Submitted That Met QC Criteria: April 25, 2008
• First Posted (ESTIMATE): April 28, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): January 20, 2012
• Last Update Submitted That Met QC Criteria: January 18, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: chronic kidney disease; hemodialysis; paricalcitol; secondary hyperparathyroidism; maxacalcitol
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Parathyroid Diseases; Neoplastic Processes; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Dermatologic Agents; Anticarcinogenic Agents; Maxacalcitol
• Other Study ID Numbers: M10-309