Pediatric Chronic Kidney Disease Safety and Efficacy

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of adding cinacalcet to the current treatment of secondary hyperparathyroidism in children currently receiving dialysis compared to a treatment regimen that does not include cinacalcet.

Detailed Description
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Secondary hyperparathyroidism (SHPT) is a condition that can develop early in patients with chronic kidney disease (CKD), usually gets worse over time, and is known to cause problems for patients on dialysis. Children on dialysis can have a wide range of bone and growth issues, and common treatments have a chance of making these things worse by increasing serum calcium and serum phosphorus. Cinacalcet has been shown to be effective in controlling parathyroid hormone (PTH), calcium and phosphorus in adults. The purpose of this study is to show that including cinacalcet in the treatment of SHPT will lower the levels of intact parathyroid hormone (iPTH) in a larger number of pediatric patients with CKD who are receiving dialysis, compared to a treatment regimen that does not include cinacalcet.

Official Title
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A Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy and Safety of Cinacalcet HCl in Pediatric Subjects With Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Dialysis

Conditions
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Chronic Kidney Disease, Hyperparathyroidism, Hyperparathyroidism, Secondary, Kidney Disease, Secondary Hyperparathyroidism

Intervention / Treatment
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* Drug: cinacalcet capsule
* Drug: placebo
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 6 to less than 18 years at screening Diagnosed with CKD and SHPT receiving hemodialysis or peritoneal dialysis for ≥ 2 months before randomization Dry weight ≥ 12.5 kg at screening iPTH obtained from the central laboratory must be > 300 pg/mL (31.8 pmol/L) Serum calcium (corrected) obtained from the central laboratory must be ≥ 8.8 mg/dL (2.2 mmol/L) Serum phosphorus obtained from the central laboratory ≥ 4.0 mg/dL (1.3 mmol/L) for children 6 to less than 12 years old, or ≥ 3.5 mg/dL (1.1 mmol/L) for children 12 to less than 18 years old Subjects already receiving vitamin D sterols (either calcitriol or a synthetic analog), a stable dose within the last 2 months prior to randomization Subjects taking growth hormone, a stable dose defined as no change > than 20% in the last 2 months prior to randomization Subjects on anti-convulsant medication must be on a stable dose for 3 months, and have a therapeutic blood level of the anti-convulsant at the time of randomization Subjects must be on a dialysate calcium concentration of ≥ 2.5 mEq/L (1.25 mmol/L) for at least 2 months prior to randomization Exclusion Criteria: Underwent parathyroidectomy in the last 6 months Anticipated parathyroidectomy within 6 months after randomization Received therapy with cinacalcet (sensipar/mimpara) within the last month A new onset of seizure or worsening of a pre-existing seizure disorder within the last 3 months Scheduled date for kidney transplant from a known living donor that makes completion of the study unlikely

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg. | Drug: placebo<br>* Placebo tablets and capsules for sprinkling identical to active treatment.<br>Drug: Standard of Care<br>* All participants, regardless of treatment assignment, will receive standard of care with vitamin D sterols (calcitriol and its analogs), as prescribed by the treating physician.<br>|
| Experimental: Cinacalcet<br>Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks. | Drug: cinacalcet capsule<br>* Cinacalcet was prepared for oral administration as both capsules for sprinkling and film coated tablets for swallowing.<br>* Other names: Sensipar, Mimpara;Drug: Standard of Care<br>* All participants, regardless of treatment assignment, will receive standard of care with vitamin D sterols (calcitriol and its analogs), as prescribed by the treating physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving ≥ 30% Reduction in Mean iPTH From Baseline to the Efficacy Assessment Phase | The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase (EAP; Weeks 25 - 30). When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available post-baseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used. | From Baseline to the Efficacy Assessment Phase, Weeks 25-30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Mean iPTH ≤ 300 pg/mL (31.8 Pmol/L) During the Efficacy Assessment Phase | The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used. | From Baseline to the Efficacy Assessment Phase (EAP), Weeks 25-30 | 
| Percent Change From Baseline in Mean Corrected Total Serum Calcium During the Efficacy Assessment Period | Serum calcium was reported as a corrected value by the central laboratory based on calcium and albumin concentrations: Corrected total calcium (mg/dL) = measured total serum calcium (mg/dL) + 0.8 (4.0 - Serum albumin (g/dL)). The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used. | From Baseline to the Efficacy Assessment Phase, Weeks 25-30. | 
| Percent Change From Baseline in Mean Serum Phosphorus During the Efficacy Assessment Phase | The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used. | From Baseline to the Efficacy Assessment Phase, Weeks 25-30. | 
| Percent Change From Baseline in Mean Phosphorous Product (Ca x P) During the Efficacy Assessment Phase | The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used. | From Baseline to end of Efficacy Assessment Period, assessed up to 30 weeks | 
| Growth Velocity From Baseline to End of Double-blind Phase | Linear growth velocity (cm/year) = 52 x change in height (cm) / number of weeks between the two assessments. End of double-blind phase visit was at Week 30 by design but the last assessment in the double-blind phase was used due to the early termination of the study. | From Baseline to end of Efficacy Assessment at Week 30 | 
| Growth Velocity From End of Double-blind Phase to End of Open-label Phase | Linear growth velocity (cm/year) = 52 x change in height (cm) / number of weeks between the two assessments. End of open-label phase visit was at Week 60 by design but the last assessment in the open-label phase was used due to the early termination of the study. | End of double-blind phase (Week 30) until end of the open-label phase (Week 60) | 
| Percent Change From Baseline in Mean Ionized Calcium During the Efficacy Assessment Phase | The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used. | From Baseline to the Efficacy Assessment Phase, Weeks 25-30. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dialysis, sensipar, mimpara, hemodialysis, peritoneal dialysis, renal, parathyroid hormone, pediatric