A Single-dose Study in Paediatric Patients Aged 2 to Less Than 18 Years With Secondary Hyperparathyroidism (sHPT) Receiving Haemodialysis

Study Overview
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Brief Summary
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This is a study to evaluate the safety and pharmacokinetics in pediatric patients with secondary hyperparathyroidism receiving a single dose of etelcalcetide at the end of hemodialysis.

Official Title
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An Open-label, Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Etelcalcetide (AMG 416) in Paediatric Subjects Aged 2 to Less Than 18 Years With Secondary Hyperparathyroidism (sHPT) Receiving Maintenance Haemodialysis

Conditions
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Chronic Kidney Disease, Secondary Hyperparathyroidism

Intervention / Treatment
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* Drug: Etelcalcetide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's parent has provided informed consent and subject has provided assent Children Age 2 to less than 18 years Diagnosed with chronic kidney disease Diagnosed with secondary hyperparathyroidism receiving hemodialysis, Weighing at least 7 kg Laboratory results within specified range. Exclusion Criteria: Currently receiving treatment in another investigation device or drug study Subject has received cinacalcet therapy within 30 days History of prolongation QT interval Subject is taking any medications that are on the QT prolongation medication list Electrocardiograph (ECG) measurements within specified range.

Ages Eligible for Study
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Minimum Age: 2 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etelcalcetide<br>Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1. | Drug: Etelcalcetide<br>* A single IV-bolus dose of 0.035 mg/kg etelcalcetide into the venous line of the dialysis circuit at the end of a hemodialysis session.<br>* Other names: Parsabiv;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Common Treatment-emergent Adverse Events | A treatment-emergent adverse event is any adverse event (AE) that begins or worsens after the initial dose of study drug (etelcalcetide) and up to 30 days after the last dose. Common adverse events were defined as adverse events occurring in at least 2 participants. The Medical Dictionary for Regulatory Activities (MedDRA) version 21.0 was used for coding all adverse events. | 30 days | 
| Change From Baseline in Serum Corrected Calcium Concentration Over Time | When albumin was less than 4.0 mg/dL, the calcium concentration was corrected according to the formula: cCa (mmol/L) = measured total serum calcium (mmol/L) + 0.02 (40 - serum albumin [g/L]). | Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study) | 
| Change From Baseline in Serum Phosphorus Concentration at End of Study |  | Baseline and day 30 (end of study) | 
| Change From Baseline in Serum Potassium Concentration at End of Study |  | Baseline and day 30 (end of study) | 
| Change From Baseline in Intact Parathyroid Hormone (iPTH) Levels Over Time |  | Baseline and day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study) | 
| Change From Baseline in Heart Rate at End of Study |  | Baseline and day 30 (end of study) | 
| Change From Baseline in Temperature at End of Study |  | Baseline and day 30 (end of study) | 
| Change From Baseline in Blood Pressure at End of Study |  | Baseline and day 30 (end of study) | 
| Change From Baseline in PR Interval at End of Study |  | Baseline and day 30 (end of study) | 
| Change From Baseline in QRS Interval at End of Study |  | Baseline and day 30 (end of study) | 
| Change From Baseline in QT Interval at End of Study |  | Baseline and day 30 (end of study) | 
| Change From Baseline in Corrected (Bazett) QT Interval at End of Study |  | Baseline and day 30 (end of study) | 
| Change From Baseline in Corrected (Fridericia) QT Interval at End of Study |  | Baseline and day 30 (end of study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Serum Total Calcium Concentration |  | Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study) | 
| Change From Baseline in Serum Ionized Calcium Concentration |  | Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study) | 
| Maximum Observed Plasma Concentration (Cmax) of Etelcalcetide | Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL. | 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose | 
| Time to Maximum Concentration (Tmax) of Etelcalcetide | Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL. | 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose | 
| Area Under the Plasma Etelcalcetide Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL. Area under the curve for plasma etelcalcetide from time zero to the last quantifiable concentration (AUClast) was estimated using the linear trapezoidal method. | 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose | 
| Area Under the Plasma Etelcalcetide Concentration-Time Curve From Time Zero Infinity (AUCinf) | Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL. Area under the concentration-time curve from time zero to infinite time (AUCinf) was estimated using the linear trapezoidal method. | 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose | 
| Terminal Half-life (T1/2,z) of Etelcalcetide | Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL. Terminal half life of plasma etelcalcetide (t1/2,z) was calculated as t1/2,z = ln(2)/λz, where λz is the first-order terminal rate constant estimated by linear regression of the terminal log-linear phase. | 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose | 
| Number of Participants Who Developed Anti-etelcalcetide Binding Antibodies | Samples were collected predose and at end of study (day 30) and tested for anti etelcalcetide binding antibodies using a validated immunoassay. Developing antibody binding was defined as participants who were binding antibody positive postbaseline with a negative result at baseline. | Baseline and day 30 | 
| Number of Participants With Treatment-emergent Adverse Events | A treatment-emergent adverse event is any adverse event that begins or worsens after the initial dose of study drug (etelcalcetide) and up to 30 days after the last dose. The severity of each adverse event was graded using the National Cancer Institute-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, where Grade 1 = Mild (asymptomatic or mild symptoms), Grade 2 = Moderate (minimal, local or noninvasive intervention indicated), Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated, Grade 4 = Life-threatening consequences; urgent intervention indicated, and Grade 5 = Death related to AE. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Secondary Hyperparathyroidism, chronic kidney disease, hemodialysis