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

Study Overview
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Brief Summary
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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.

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

Conditions
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Secondary Hyperparathyroidism, Hemodialysis

Intervention / Treatment
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* Drug: paricalcitol
* Drug: maxacalcitol
* Drug: paricalcitol placebo
* Drug: maxacalcitol placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paricalcitol<br>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<br> <br> * Other names: Zemplar;Drug: maxacalcitol placebo<br> <br> |
| Active Comparator: Maxacalcitol<br>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<br> <br> * Other names: oxarol;Drug: paricalcitol placebo<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Secondary hyperparathyroidism, Paricalcitol, Hemodialysis, Maxacalcitol