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

This study has been completed.
Sponsor:
Collaborator:
Abbott Japan Co.,Ltd
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00667576
First received: April 24, 2008
Last updated: January 18, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Chronic Kidney Disease on Hemodialysis
Secondary Hyperparathyroidism
Drug: Maxacalcitol
Drug: Paricalcitol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Abbott:

Primary Outcome Measures:
  • Percentage of Subjects With ≥ 50% Decrease From Baseline in Intact Parathyroid Hormone (iPTH) Serum Level [ Time Frame: Baseline to Week 13 (Final Visit) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean Change From Baseline in Intact Parathyroid Hormone (iPTH) Level [ Time Frame: Baseline to Week 13 (Final Visit) ] [ Designated as safety issue: No ]
  • Percentage of Subjects With Intact Parathyroid Hormone (iPTH) ≤ 180 Picograms/Milliliter (pg/mL) [ Time Frame: Baseline to Week 13 (Final Visit) ] [ Designated as safety issue: No ]
  • Percentage of Subjects With 2 or More Decreases of ≥ 50% From Baseline in Intact Parathyroid Hormone (iPTH) Level [ Time Frame: Through Week 13 ] [ Designated as safety issue: No ]
  • Duration of 2 Consecutive Decreases of ≥ 50% From Baseline in Intact Parathyroid Hormone (iPTH) Values [ Time Frame: Through Week 13 ] [ Designated as safety issue: No ]
  • Duration of 2 Consecutive Intact Parathyroid Hormone (iPTH) Values ≤ 180 pg/mL [ Time Frame: Through Week 13 ] [ Designated as safety issue: No ]

Enrollment: 153
Study Start Date: April 2008
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • ABT-358
  • Zemplar
  • paricalcitol
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:
  • ABT-358
  • Zemplar
  • paricalcitol
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:
  • ABT-358
  • Zemplar
  • paricalcitol
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:
  • ABT-358
  • Zemplar
  • paricalcitol
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.
Other Name: 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).

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00667576

Locations
Japan
Tokyo, Metropolis, Japan
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
Sponsors and Collaborators
Abbott
Abbott Japan Co.,Ltd
Investigators
Study Director: Ryotaro Matsuzawa Abbott
  More Information

No publications provided

Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT00667576     History of Changes
Other Study ID Numbers: M10-309
Study First Received: April 24, 2008
Results First Received: March 18, 2010
Last Updated: January 18, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Abbott:
chronic kidney disease
secondary hyperparathyroidism
hemodialysis
paricalcitol
maxacalcitol

Additional relevant MeSH terms:
Hyperparathyroidism
Hyperparathyroidism, Secondary
Kidney Diseases
Renal Insufficiency, Chronic
Parathyroid Diseases
Endocrine System Diseases
Urologic Diseases
Renal Insufficiency
Maxacalcitol
Calcitriol
Ergocalciferols
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Cardiovascular Agents
Vitamins
Micronutrients
Growth Substances
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 28, 2014