Comparison of Efficacy and Safety of Paricalcitol Injection With Maxacalcitol Injection in Adult Japanese Chronic Kidney Disease Subjects Receiving Hemodialysis With Secondary Hyperparathyroidism

This study is a comparison of the efficacy and safety of paricalcitol injection with maxacalcitol injection in adult Japanese chronic kidney disease patients receiving hemodialysis with secondary hyperparathyroidism. The main objective of this study is to demonstrate the efficacy of paricalcitol injection in reducing levels of parathyroid hormone without clinically significant hypercalcemia, compared to maxacalcitol injection.

Study Overview

• Status: Completed
• Conditions: Hemodialysis; Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: paricalcitol; Drug: maxacalcitol placebo; Drug: maxacalcitol; Drug: paricalcitol placebo

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
    • Site Reference ID/Investigator# 53485
  • Chiba, Japan
    • Site Reference ID/Investigator# 51571
  • Chiba, Japan
    • Site Reference ID/Investigator# 52963
  • Chiba, Japan
    • Site Reference ID/Investigator# 52966
  • Gifu, Japan
    • Site Reference ID/Investigator# 51578
  • Gunma, Japan
    • Site Reference ID/Investigator# 52965
  • Hadano-City, Japan
    • Site Reference ID/Investigator# 53782
  • Himeji-City, Japan
    • Site Reference ID/Investigator# 57483
  • Hokkaido, Japan
    • Site Reference ID/Investigator# 57487
  • Hyogo, Japan
    • Site Reference ID/Investigator# 53484
  • Ibaraki, Japan
    • Site Reference ID/Investigator# 54385
  • Kagawa, Japan
    • Site Reference ID/Investigator# 51581
  • Kagoshima, Japan
    • Site Reference ID/Investigator# 59164
  • Kanagawa, Japan
    • Site Reference ID/Investigator# 51574
  • Kanagawa, Japan
    • Site Reference ID/Investigator# 51575
  • Kodaira, Japan
    • Site Reference ID/Investigator# 52751
  • Koga, Japan
    • Site Reference ID/Investigator# 62025
  • Matsumoto, Japan
    • Site Reference ID/Investigator# 54384
  • Midori, Japan
    • Site Reference ID/Investigator# 52745
  • Mito, Japan
    • Site Reference ID/Investigator# 51569
  • Nagano, Japan
    • Site Reference ID/Investigator# 52964
  • Nagano, Japan
    • Site Reference ID/Investigator# 53483
  • Nagasaki, Japan
    • Site Reference ID/Investigator# 51582
  • Nagoya, Japan
    • Site Reference ID/Investigator# 54388
  • Niigata, Japan
    • Site Reference ID/Investigator# 51576
  • Niigata, Japan
    • Site Reference ID/Investigator# 51577
  • Osaka, Japan
    • Site Reference ID/Investigator# 51580
  • Osaka, Japan
    • Site Reference ID/Investigator# 52747
  • Osaka, Japan
    • Site Reference ID/Investigator# 52748
  • Osaka, Japan
    • Site Reference ID/Investigator# 52750
  • Saitama, Japan
    • Site Reference ID/Investigator# 51570
  • Sakai, Japan
    • Site Reference ID/Investigator# 54387
  • Sapporo, Japan
    • Site Reference ID/Investigator# 52746
  • Shizuoka, Japan
    • Site Reference ID/Investigator# 51579
  • Takasaki, Japan
    • Site Reference ID/Investigator# 62024
  • Tokyo, Japan
    • Site Reference ID/Investigator# 51572
  • Tokyo, Japan
    • Site Reference ID/Investigator# 52752
  • Tokyo, Japan
    • Site Reference ID/Investigator# 53482
  • Tokyo, Japan
    • Site Reference ID/Investigator# 59162
  • Tokyo, Japan
    • Site Reference ID/Investigator# 59966
  • Tomakomai-shi, Japan
    • Site Reference ID/Investigator# 53783
  • Toyama, Japan
    • Site Reference ID/Investigator# 54383
  • Wakayama, Japan
    • Site Reference ID/Investigator# 52749
  • Yachiyoshi, Japan
    • Site Reference ID/Investigator# 52962
  • Yokohama-Shi, Japan
    • Site Reference ID/Investigator# 59163

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:

• Adult Chronic Kidney Disease (CKD) Stage 5 patients undergoing dialysis with stable dialysate calcium and phosphate binders
• On three times weekly hemodialysis for at least 3 months prior with intact parathyroid hormone (iPTH) greater than or equal to 300 pg/mL, adjusted normalized serum total calcium (Ca) greater than or equal to 8.4 to less than 10.2 mg/dL, serum phosphorus (P) less than or equal to 6.5 mg/dL.

Exclusion Criteria:

• Patients with a recent history of severe cardiovascular or hepatic disease, uncontrolled hypertension or uncontrolled diabetes
• Patients who have received a parathyroidectomy or ethanol infusion within the prior year
• Patients taking drugs that affect iPTH, calcium or bone metabolism
• Patients who will need to take chronic doses (greater than or equal to 2 consecutive weeks) of cytochrome P450 inhibitors (e.g., clarithromycin, grapefruit products) or inducers (e.g., carbamazepine, rifampicin)
• Female patients who are pregnant, possibly pregnant, wish to become pregnant, or participate in breastfeeding during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paricalcitol; Participants received paricalcitol at an initial dose of 2 µg, and maxacalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 1 µg based on protocol-specified criteria up to a maximum of 7 µg.	Drug: paricalcitol; Other Names: Zemplar; ABT-358; Drug: maxacalcitol placebo
Active Comparator: Maxacalcitol; Participants received maxacalcitol at an initial dose of 5 µg (iPTH < 500 pg/mL at Screening) or 10 µg (iPTH ≥ 500 pg/mL at Screening), and paricalcitol placebo administered 3 times per week at each hemodialysis via intravenous catheter for 12 weeks. After 2 weeks the dose could be adjusted ± 2.5 µg based on protocol-specified criteria up to a maximum of 20 µg.	Drug: maxacalcitol; Other Names: oxarol; Drug: paricalcitol placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Target Intact Parathyroid Hormone (iPTH) and Without Hypercalcemia	The target iPTH range was 60-180 pg/mL, based on the average of the last 3 weeks of treatment, and with no hypercalcemia during the treatment phase. Hypercalcemia was defined as at least 1 corrected calcium value > 11.0 mg/dL or at least 2 corrected calcium values ≥ 10.5 mg/dL. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory.	iPTH measured during the last three weeks of treatment (Weeks 11, 12, and 13). Calcium measured throughout the study (Weeks 1-13).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline and With No Hypercalcemia	The percentage of participants with greater than or equal to 50% reduction in intact parathyroid hormone (iPTH) from baseline to the average of the last 3 weeks of treatment and with no hypercalcemia during the treatment phase. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory. Hypercalcemia was defined as at least 1 corrected calcium value > 11.0 mg/dL or at least 2 corrected calcium values ≥ 10.5 mg/dL.	Baseline to the last three weeks of treatment (Weeks 11, 12, and 13) for iPTH. Calcium measured throughout the study (Weeks 1-13).
Percentage of Participants With Target Intact Parathyroid Hormone (iPTH)	The target iPTH range was 60-180 pg/mL, based on the average of the last 3 weeks of treatment. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory.	The last three weeks of treatment (Weeks 11, 12, and 13)
Percentage of Participants With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline	The percentage of participants with a greater than or equal to 50% reduction in intact parathyroid hormone (iPTH) from baseline to the average of the last 3 weeks of treatment. iPTH was measured before the first dialysis session of each week and analyzed by the central laboratory.	Baseline to the last three weeks of treatment (Weeks 11, 12, and 13)
Number of Visits at Which Participants Achieved iPTH Control With ≥ 50% Reduction in Intact Parathyroid Hormone (iPTH) From Baseline	iPTH control was defined as a ≥ 50% reduction from baseline. iPTH was measured before the first dialysis session of the week, each week during the treatment phase and analyzed by the central laboratory.	Weeks 2 to 13
Number of Visits at Which Participants Achieved iPTH Control in the Target Range of 60 to 180 pg/mL	iPTH control was defined as being within the target range of 60 to 180 pg/mL. iPTH was measured before the first dialysis session of the week, once a week during the treatment phase and analyzed by the central laboratory.	Weeks 2 to 13

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)
• Investigators: Study Director: Kazuya Kobayashi, BA, AbbVie GK.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: April 25, 2011
• First Submitted That Met QC Criteria: April 25, 2011
• First Posted (Estimate): April 26, 2011

Study Record Updates

• Last Update Posted (Estimate): June 6, 2013
• Last Update Submitted That Met QC Criteria: April 17, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Dermatologic Agents; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Anticarcinogenic Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Ergocalciferols; Calcitriol; Maxacalcitol
• Other Study ID Numbers: M11-517