Safety and Efficacy of Hectorol in Pediatric Patients With Chronic Kidney Disease Stage 3 and 4 With Secondary Hyperparathyroidism Not Yet on Dialysis

Study Overview
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Brief Summary
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Primary Objective: Evaluate the effect of Hectorol® capsules in reducing elevated levels of intact parathyroid hormone (iPTH). Secondary Objectives: Evaluate the safety profile of Hectorol® capsules versus Rocaltrol® (calcitriol) capsules. Determine the pharmacokinetic profile of 1,25-dihydroxyvitamin D2 after administration of Hectorol®.

Detailed Description
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The total study duration per patient will be approximately up to 28 weeks.

Official Title
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An Open-Label, Randomized, Parallel Group Study to Assess the Safety and Efficacy of Hectorol® (Doxercalciferol Capsules) in Pediatric Patients With Chronic Kidney Disease Stages 3 and 4 With Secondary Hyperparathyroidism Not Yet on Dialysis

Conditions
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Secondary Hyperparathyroidism-Chronic Kidney Disease

Intervention / Treatment
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* Drug: Doxercalciferol (GZ427397)
* Drug: Calcitriol


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Male or female aged 5 to 18 years old. Weight ≥15 kg. Chronic kidney disease (CKD) Stage 3 or 4 not on dialysis, defined as glomerular filtration rate (GFR) between 15 and 59 mL/min/1.73m^2 (established by Schwartz equation) at Week -2 visit. Intact parathyroid hormone (iPTH) value >100 pg/mL for CKD Stage 3 or >160 pg/mL for CKD Stage 4, at Week -2 visit. Signed informed consent/assent form. Exclusion criteria: The patient has a serum 25-hydroxyvitamin D level <30 ng/mL at screening. The patient has a corrected calcium ≥10 mg/dL at the Week -2 visit. The patient has a serum phosphorus >4.5 mg/dL for children 13 to 18 years of age; >5.8 mg/dL for children 5 to 12 years of age at the Week -2 visit. The patient is anticipated to require maintenance hemodialysis within 3 months. The patient used cinacalcet or vitamin D sterol therapies such as calcitriol, doxercalciferol, or paricalcitol within 14 days prior to the baseline visit. The patient has a history of, or active, symptomatic heart disease within 12 months prior to the baseline (Week 0) visit. The patient currently has a chronic gastrointestinal disease (ie, malabsorption, severe chronic diarrhea, chronic ulcerative colitis, or ileostomy). The patient currently has primary hyperparathyroidism or has had a total parathyroidectomy. The patient has an active malignancy. The patient is unable to swallow a capsule in size similar to the Hectorol® and Rocaltrol® capsules. The patient has a history of sensitivity or allergy to doxercalciferol, calcitriol or other vitamin D analogs. The patient currently uses aluminum or magnesium-based binders. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hectorol<br>Hectorol (Doxercalciferol) will be administered orally two to three times weekly dependent on patient age. A dose titration scheme is used to individualize the dose to the patient's iPTH management. | Drug: Doxercalciferol (GZ427397)<br>* Pharmaceutical form: capsule Route of administration: oral<br>* Other names: Hectorol;|
| Active Comparator: Rocaltrol<br>Rocaltrol (Calcitriol) will be administered orally seven days/week. A dose titration scheme is used to individualize the dose to the patient's iPTH management. | Drug: Calcitriol<br>* Pharmaceutical form: capsule Route of administration: oral<br>* Other names: Rocaltrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving two consecutive ≥30% reductions in iPTH |  | Baseline up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline in iPTH |  | Baseline, Week 12, Week 24 | 
| Number of hypercalcemia events (albumin corrected serum calcium >10.2 mg/dL) |  | Up to Weeks 12 and 24 | 
| Number of participants with adverse events |  | Baseline up to Week 24 | 
| Assessment of pharmacokinetic (PK) parameter: Serum 1,25-dihydroxyvitamin D2 concentration-time data |  | At Week -2, Baseline, and then within 24 hours of the most recent dose of Hectorol® at Weeks 2, 4, 6, 8 or 10 (whichever week is not used for serial PK assessment), and 12 |