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

Phase 1
Completed
Conditions
Chronic Kidney Disease, Secondary Hyperparathyroidism
Interventions
Registration Number
NCT02833857
Lead Sponsor
Amgen
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
11
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
EtelcalcetideEtelcalcetideParticipants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in QT Interval at End of StudyBaseline and day 30 (end of study)
Change From Baseline in Serum Potassium Concentration at End of StudyBaseline and day 30 (end of study)
Change From Baseline in Intact Parathyroid Hormone (iPTH) Levels Over TimeBaseline and day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)
Change From Baseline in Blood Pressure at End of StudyBaseline and day 30 (end of study)
Change From Baseline in PR Interval at End of StudyBaseline and day 30 (end of study)
Change From Baseline in QRS Interval at End of StudyBaseline and day 30 (end of study)
Common Treatment-emergent Adverse Events30 days

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.

Change From Baseline in Heart Rate at End of StudyBaseline and day 30 (end of study)
Change From Baseline in Serum Corrected Calcium Concentration Over TimeBaseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)

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 \[g/L\]).

Change From Baseline in Temperature at End of StudyBaseline and day 30 (end of study)
Change From Baseline in Serum Phosphorus Concentration at End of StudyBaseline and day 30 (end of study)
Change From Baseline in Corrected (Bazett) QT Interval at End of StudyBaseline and day 30 (end of study)
Change From Baseline in Corrected (Fridericia) QT Interval at End of StudyBaseline and day 30 (end of study)
Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Serum Ionized Calcium ConcentrationBaseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)
Change From Baseline in Serum Total Calcium ConcentrationBaseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)
Maximum Observed Plasma Concentration (Cmax) of Etelcalcetide10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose

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 (T1/2,z) of Etelcalcetide10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose

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.

Number of Participants Who Developed Anti-etelcalcetide Binding AntibodiesBaseline and day 30

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.

Time to Maximum Concentration (Tmax) of Etelcalcetide10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose

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 Plasma Etelcalcetide Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose

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.

Number of Participants With Treatment-emergent Adverse Events30 days

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.

Area Under the Plasma Etelcalcetide Concentration-Time Curve From Time Zero Infinity (AUCinf)10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose

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.

Trial Locations

Locations (1)

Research Site

🇬🇧

London, United Kingdom

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