Safety & Tolerability of Cinacalcet in Pediatric Patients With Chronic Kidney Disease and Secondary Hyperparathyroidism

Study Overview
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Brief Summary
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The primary objective was to characterize corrected serum calcium levels on treatment with cinacalcet in pediatric patients with secondary hyperparathyroidism (HPT).

Detailed Description
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This is a multicenter, 26-week, single-arm, open-label, safety study. Participants were to remain on study for 26 weeks or until time of kidney transplantation, whichever came first. The study and enrollment was placed on partial clinical hold in February 2013 which resulted in changes to the protocol. The study was restarted in April 2014 following these changes. Participants who completed the 26-week study or were on study when the study was closed in June 2016 were eligible to participate in an open-label extension study (Study 20140159; NCT02341417).

Official Title
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An Open-label, Single-arm Study to Assess the Safety & Tolerability of Cinacalcet in Addition to Standard of Care in Pediatric Subjects Age 28 Days to < 6 Yrs With Chronic Kidney Disease & Secondary Hyperparathyroidism Receiving Dialysis

Conditions
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Chronic Kidney Disease, Hyperparathyroidism, Secondary

Intervention / Treatment
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* Drug: Cinacalcet hydrochloride
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects between the ages of 28 days to < 6 years of age at enrollment (Czech Republic minimum age is ≥ 2 years of age at enrollment) Screening plasma iPTH level > 300 pg/mL (31.8 pmol/L) from the central laboratory, and not have received any cinacalcet therapy for at least 30 days prior to start of dosing Screening corrected calcium from the central laboratory: ≥ 9.4 mg/dL (2.35 mmol/L) if age 28 days to < 2 years ≥ 8.8 (2.2 mmol/L) if age ≥ 2 to < 6 years Serum phosphorus from the central laboratory: ≥ 5.0 mg/dL (1.25 mmol/L) if age 28 days to < 1 year ≥ 4.5 mg/dL (1.13 mmol/L) if age ≥ 1 to < 6 years SHPT not due to vitamin D deficiency, per investigator assessment Dry weight ≥ 7 kg at the time of screening Exclusion criterion: History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrhythmias or other conditions associated with prolonged QT interval Corrected QT interval (QTc) > 500 ms, using Bazett's formula QTc ≥ 450 to ≤ 500 ms, using Bazett's formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist Use of grapefruit juice, herbal medications, or potent CYP 3A4 inhibitors (e.g., erythromycin, clarithromycin, ketoconazole, itraconazole) Use of concomitant medications that may prolong the QTc interval (e.g., ondansetron, albuterol)

Ages Eligible for Study
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Minimum Age: 28 Days
Maximum Age: 2189 Days

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cinacalcet<br>Prior to the partial clinical hold, the starting dose was 0.25 mg/kg (based on dry weight) and was titrated upwards (maximum allowed daily dose of 4.2 mg/kg) based on plasma intact parathyroid hormone (iPTH), corrected serum calcium levels obtained monthly, and adverse signs and symptoms. After the partial clinical hold the starting dose was 0.20 mg/kg (based on dry weight) and was titrated upwards (maximum allowed daily dose of 2.5 or 60 mg, whichever was lower) based on plasma iPTH, corrected serum calcium levels obtained monthly, weekly monitoring of ionized calcium levels, and adverse signs and symptoms. All participants also received standard of care, which may have included vitamin D sterols. | Drug: Cinacalcet hydrochloride<br>* Cinacalcet was provided as 5 mg capsules that were opened, and the contents were either sprinkled on soft food or suspended into a sucrose syrup to create a liquid suspension for administration. All doses were administered with food or shortly after a meal at the same time daily.<br>* Other names: Mimpara®;Drug: Standard of Care<br>* Standard of care may have included vitamin D sterols (25 OH vitamin D and/or 1-25 OH vitamin D and its analogs) at the discretion of the investigator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hypocalcemia | Hypocalcemia was defined as corrected serum calcium levels < 9.0 mg/dL (2.25 mmol/L) for participants aged 28 days to < 2 years, and < 8.4 mg/dL (2.1 mmol/L) for participants aged ≥ 2 years to < 6 years at any time during the study. | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Corrected Serum Calcium Levels < 8.8 mg/dL (2.2 mmol/L) During the Study |  | 26 weeks | 
| Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) |  | Baseline and weeks 3, 7, 11, 15, 19, 22, and 24 | 
| Percent Change From Baseline in Corrected Serum Calcium |  | Baseline and weeks 3, 7, 11, 15, 19, 22, and 24 | 
| Percent Change From Baseline in Serum Phosphorous |  | Baseline and weeks 3, 7, 11, 15, 19, 22, and 24 | 
| Percent Change From Baseline in Calcium Phosphorus Product (Ca x P) |  | Baseline and weeks 3, 7, 11, 15, 19, 22, and 24 | 
| Percentage of Participants Who Achieved > 30% Reduction in iPTH From Baseline at Any Two Consecutive Measurements | A participant was considered to have achieved > 30% reduction in iPTH from baseline at any 2 consecutive measurements if percent change of any two consecutive post-baseline iPTH values were < -30% regardless if there was a missing value in between. | 26 weeks | 
| Percentage of Participants Who Achieved ≥ 30% Reduction in iPTH From Baseline During the Study | A participant was considered to have achieved ≥ 30% reduction in iPTH if the percent change of any post-baseline iPTH value was ≤ -30% from baseline. | 26 weeks | 
| Percentage of Participants Who Achieved iPTH Values Between 200 and 300 pg/mL at Any Two Consecutive Measurements | A participant was considered to have achieved iPTH between 200 and 300 pg/mL (21.2 and 31.8 pmol/L) at any 2 consecutive measurements if any two consecutive post-baseline iPTH values were within the range regardless if there was a missing value in between. The analysis included all enrolled subjects with at least 1 post-baseline assessment. | 26 weeks | 
| Percentage of Participants Who Achieved iPTH Values < 300 pg/mL During the Study | A participant was considered to have achieved iPTH < 300 pg/mL (31.8 pmol/L) during the study if any post-baseline iPTH value was < 300 pg/mL. | 26 weeks | 
| Dose- and Weight-Normalized Maximum Plasma Concentration (Cmax) of Cinacalcet |  | Week 12 | 
| Dose- and Weight-Normalized Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Cinacalcet |  | Week 12 | 

 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