This was a multiple-dose, double-blind, randomized, placebo-controlled study. Chinese subjects residing in Mainland China with chronic kidney disease (CKD) receiving hemodialysis were randomized in a 3:1 ratio to receive 5 mg intravenous (IV) of etelcalcetide or placebo 3 times a week (TIW) for approximately 4 weeks, with a subsequent follow up period of approximately 4 weeks. Doses were given at the end of each scheduled hemodialysis session on study days 1 through day 27 and subject participation was complete after day 55 end-of-study (EOS) procedures were performed. Doses were administered TIW for 4 weeks, for a total of 12 doses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
33
Etelcalcetide was supplied as a sterile, preservative-free, aqueous solution in a single-use 3 mL glass vial.
Placebo supplied to match active intervention.
Research Site
Beijing, Beijing Municipality, China
Research Site
Nanjing, Jiangsu, China
Research Site
Shanghai, Shanghai Municipality, China
Research Site
Shanghai, Shanghai Municipality, China
Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27
Tmax is the time to maximum drug concentration of plasma etelcalcetide after dosing on Days 1 and 27.
Time frame: Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27
Cmax was defined as the maximum observed plasma drug concentration measured between the time of drug administration to the beginning of the next dialysis session.
Time frame: Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27
AUClast was specifically defined in this study as the area under the concentration time curve measured from the time of drug administration to the beginning of the next dialysis session, following the first and last dose.
Time frame: Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27
Accumulation ratio, calculated as AUClast day 27/AUClast day 1.
Time frame: Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
Participants With Treatment-Emergent Adverse Events (TEAEs)
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Research Site
Shanghai, Shanghai Municipality, China
The severity of each adverse event was assessed using the NCI-CTCAE Version 4.0 according to the following: * Grade 1 - Mild: Asymptomatic or mild symptoms; intervention not indicated * Grade 2 - Moderate: Minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) * Grade 3 - Severe: Medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL * Grade 4 - Life-threatening * Grade 5 - Fatal. A serious AE is an AE that met one or more of the following criteria: * Death * Life-threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * A congenital anomaly/birth defect * Important medical events that required medical or surgical intervention to prevent one of the outcomes above.
Time frame: Day 1 up to Day 55 (end of study)
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
Terms were coded with Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. Narrow search criteria used for both standardized MedDRA queries (SMQ) and events of interest (EOI). One preferred term (PT) could match multiple EOIs. Infusion Reaction EOI counts included only those events which had onset day coinciding with study medication infusion and resolved on the same day or the day after onset.
Time frame: Day 1 up to Day 55 (end of study)
Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study
Count of participants who exhibited a clinically significant change in the results of their 12-lead electrocardiograms (ECG) when comparing baseline to end of study ECGs.
Time frame: Baseline is Day -2; End of Study is Day 55
Change From Baseline to End of Study in Weight
Change from baseline in weight measured at visit.
Time frame: Day 1 up to Day 55
Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures
Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.
Time frame: Baseline Day 1 prior to dialysis; End of Study is Day 55
Baseline and Change From Baseline to End of Study in Heart Rate
Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.
Time frame: Baseline Day 1 prior to dialysis; End of Study is Day 55
Change From Baseline to End of Study in Calcium
Calcium was tested at a central laboratory.
Time frame: Baseline is Day 1 prior to dialysis; End of Study is Day 55
Change From Baseline to End of Study in Corrected Calcium (cCa)
Total serum calcium was corrected if the serum albumin was \< 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium. The correction formula was: Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin \[g/dL\]) \* 0.8
Time frame: Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
Participants With Low Corrected Calcium (cCA) By Category
The lowest cCA value for each participant is reported. Total serum calcium was corrected if the serum albumin was \< 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium. The correction formula was: Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin \[g/dL\]) \* 0.8
Time frame: Timeframes: Days 8, 15, 22, 27, 29, 34, 41, 55
Baseline and Change From Baseline to End of Study in Serum Albumin
Serum albumin was tested at a central laboratory.
Time frame: Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
Change From Baseline to End of Study in Serum Phosphorus
Serum phosphorus was tested at a central laboratory.
Time frame: Baseline is Day 1 prior to dialysis; End of Study is Day 55
Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline
Participants with positive titers for antibodies to etelcalcetide could be asked to return to the clinical research unit to provide additional serum samples.
Time frame: Baseline: Day 1 prior to dialysis. Postbaseline: Days 29 and 55 prior to dialysis