Trial Outcomes & Findings for A Single-dose Study in Paediatric Patients Aged 2 to Less Than 18 Years With Secondary Hyperparathyroidism (sHPT) Receiving Haemodialysis (NCT NCT02833857)

NCT ID: NCT02833857

Last Updated: 2019-07-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 11 participants
• Primary outcome timeframe: 30 days
• Results posted on: 2019-07-10

Participant Flow

This study was conducted at 6 centers in the United States, United Kingdom, and the European Union. Participants were enrolled from 14 March 2017 to 01 October 2018.

Participant milestones

Measure	Etelcalcetide Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Overall Study STARTED	11
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Participants with available data

Baseline characteristics by cohort

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Age, Continuous	10.3 years STANDARD_DEVIATION 4.3 • n=11 Participants
Age, Customized Children (2 to 11 years)	5 Participants n=11 Participants
Age, Customized Adolescents (12 to 17 years)	6 Participants n=11 Participants
Sex: Female, Male Female	6 Participants n=11 Participants
Sex: Female, Male Male	5 Participants n=11 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=11 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=11 Participants
Race/Ethnicity, Customized Black (or African American)	2 Participants n=11 Participants
Race/Ethnicity, Customized White	9 Participants n=11 Participants
Serum Corrected Calcium Concentration	2.42 mmol/L STANDARD_DEVIATION 0.08 • n=11 Participants
Serum Phosphorus Concentration	1.79 mmol/L STANDARD_DEVIATION 0.45 • n=10 Participants • Participants with available data
Serum Potassium Concentration	4.77 mmol/L STANDARD_DEVIATION 0.55 • n=11 Participants
Serum Intact Parathyroid Hormone Concentration	66.10 pmol/L STANDARD_DEVIATION 57.57 • n=11 Participants
Serum Calcium Concentration	2.41 mmol/L STANDARD_DEVIATION 0.08 • n=11 Participants
Serum Ionized Calcium Concentration	1.16 mmol/L STANDARD_DEVIATION 0.07 • n=11 Participants
Heart Rate	87.4 beats/minute STANDARD_DEVIATION 9.9 • n=11 Participants
Temperature	36.6 degrees celsius STANDARD_DEVIATION 0.3 • n=11 Participants
Blood Pressure Systolic blood pressure	119.4 mmHg STANDARD_DEVIATION 15.9 • n=11 Participants
Blood Pressure Diastolic blood pressure	66.7 mmHg STANDARD_DEVIATION 15.1 • n=11 Participants
PR Interval	133.8 ms STANDARD_DEVIATION 8.7 • n=11 Participants
QRS Interval	82.0 ms STANDARD_DEVIATION 10.9 • n=11 Participants
QT Interval	363.5 ms STANDARD_DEVIATION 26.2 • n=11 Participants
Corrected (Bazett) QT Interval (QTcB)	424.2 ms STANDARD_DEVIATION 29.1 • n=11 Participants
Corrected (Fridericia) QT Interval (QTcF)	402.7 ms STANDARD_DEVIATION 26.1 • n=11 Participants

PRIMARY outcome

Timeframe: 30 days

Population: Participants who received at least 1 dose of etelcalcetide (safety analysis set)

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.

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Common Treatment-emergent Adverse Events Headache	2 Participants
Common Treatment-emergent Adverse Events Calcium ionised decreased	2 Participants
Common Treatment-emergent Adverse Events Hypotension	2 Participants

PRIMARY outcome

Timeframe: Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)

Population: Treated participants with available data at each time point.

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]).

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in Serum Corrected Calcium Concentration Over Time Day 1, 4 hours	-0.03 mmol/L Standard Deviation 0.12
Change From Baseline in Serum Corrected Calcium Concentration Over Time Day 3	-0.03 mmol/L Standard Deviation 0.08
Change From Baseline in Serum Corrected Calcium Concentration Over Time Day 8	0.03 mmol/L Standard Deviation 0.09
Change From Baseline in Serum Corrected Calcium Concentration Over Time Day 10	0.03 mmol/L Standard Deviation 0.07
Change From Baseline in Serum Corrected Calcium Concentration Over Time Day 30	-0.01 mmol/L Standard Deviation 0.16

PRIMARY outcome

Timeframe: Baseline and day 30 (end of study)

Population: Treated participants

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in Serum Phosphorus Concentration at End of Study	0.08 mmol/L Standard Deviation 0.31

PRIMARY outcome

Timeframe: Baseline and day 30 (end of study)

Population: Treated participants

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in Serum Potassium Concentration at End of Study	0.45 mmol/L Standard Deviation 1.21

PRIMARY outcome

Timeframe: Baseline and day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)

Population: Treated participants with available data at each time point.

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in Intact Parathyroid Hormone (iPTH) Levels Over Time Day 1, 4 hours	-29.44 pmol/L Standard Deviation 37.16
Change From Baseline in Intact Parathyroid Hormone (iPTH) Levels Over Time Day 3	-14.81 pmol/L Standard Deviation 37.81
Change From Baseline in Intact Parathyroid Hormone (iPTH) Levels Over Time Day 8	-10.20 pmol/L Standard Deviation 38.16
Change From Baseline in Intact Parathyroid Hormone (iPTH) Levels Over Time Day 10	-4.68 pmol/L Standard Deviation 37.92
Change From Baseline in Intact Parathyroid Hormone (iPTH) Levels Over Time Day 30	-19.81 pmol/L Standard Deviation 51.29

PRIMARY outcome

Timeframe: Baseline and day 30 (end of study)

Population: Treated participants

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in Heart Rate at End of Study	-4.5 beats/minute Standard Deviation 9.3

PRIMARY outcome

Timeframe: Baseline and day 30 (end of study)

Population: Treated participants

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in Temperature at End of Study	0.1 degrees celsius Standard Deviation 0.4

PRIMARY outcome

Timeframe: Baseline and day 30 (end of study)

Population: Treated participants

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in Blood Pressure at End of Study Systolic blood pressure	0.2 mmHg Standard Deviation 17.5
Change From Baseline in Blood Pressure at End of Study Diastolic blood pressure	3.8 mmHg Standard Deviation 8.5

PRIMARY outcome

Timeframe: Baseline and day 30 (end of study)

Population: Treated participants

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in PR Interval at End of Study	-3.6 ms Standard Deviation 13.9

PRIMARY outcome

Timeframe: Baseline and day 30 (end of study)

Population: Treated participants

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in QRS Interval at End of Study	-2.6 ms Standard Deviation 6.8

PRIMARY outcome

Timeframe: Baseline and day 30 (end of study)

Population: Treated participants

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in QT Interval at End of Study	2.8 ms Standard Deviation 21.6

PRIMARY outcome

Timeframe: Baseline and day 30 (end of study)

Population: Treated participants

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in Corrected (Bazett) QT Interval at End of Study	-2.1 ms Standard Deviation 32.2

PRIMARY outcome

Timeframe: Baseline and day 30 (end of study)

Population: Treated participants

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in Corrected (Fridericia) QT Interval at End of Study	-0.5 ms Standard Deviation 23.3

SECONDARY outcome

Timeframe: Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)

Population: Treated participants with available data at each time point.

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in Serum Total Calcium Concentration Day 1, 4 hours	-0.02 mmol/L Standard Deviation 0.12
Change From Baseline in Serum Total Calcium Concentration Day 3	-0.02 mmol/L Standard Deviation 0.08
Change From Baseline in Serum Total Calcium Concentration Day 8	0.03 mmol/L Standard Deviation 0.08
Change From Baseline in Serum Total Calcium Concentration Day 10	0.02 mmol/L Standard Deviation 0.08
Change From Baseline in Serum Total Calcium Concentration Day 30	-0.01 mmol/L Standard Deviation 0.16

SECONDARY outcome

Timeframe: Baseline and Day 1, 4 hours postdose, day 3, day 8, day 10, and day 30 (end of study)

Population: Treated participants with available data at each time point.

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Change From Baseline in Serum Ionized Calcium Concentration Day 1, 4 hours	-0.05 mmol/L Standard Deviation 0.13
Change From Baseline in Serum Ionized Calcium Concentration Day 3	-0.01 mmol/L Standard Deviation 0.08
Change From Baseline in Serum Ionized Calcium Concentration Day 8	0.02 mmol/L Standard Deviation 0.07
Change From Baseline in Serum Ionized Calcium Concentration Day 10	0.01 mmol/L Standard Deviation 0.06
Change From Baseline in Serum Ionized Calcium Concentration Day 30	0.03 mmol/L Standard Deviation 0.06

SECONDARY outcome

Timeframe: 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose

Population: The pharmacokinetic analysis set

Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL.

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Maximum Observed Plasma Concentration (Cmax) of Etelcalcetide	50.8 ng/mL Standard Deviation 29.3

SECONDARY outcome

Timeframe: 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose

Population: The pharmacokinetic concentration analysis set was composed of all participants who received etelcalcetide and had at least 1 pharmacokinetic sample collected.

Plasma etelcalcetide concentrations were measured using a validated high performance liquid chromatography assay. The lower limit of quantitation was 0.200 ng/mL.

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Time to Maximum Concentration (Tmax) of Etelcalcetide	0.17 hours Interval 0.17 to 0.33

SECONDARY outcome

Timeframe: 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose

Population: Pharmacokinetic analysis set

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.

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Area Under the Plasma Etelcalcetide Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)	1360 hr*ng/mL Standard Deviation 1110

SECONDARY outcome

Timeframe: 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose

Population: Pharmacokinetic analysis set with available AUCinf data

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.

Outcome measures

Measure	Etelcalcetide n=7 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Area Under the Plasma Etelcalcetide Concentration-Time Curve From Time Zero Infinity (AUCinf)	1700 hr*ng/mL Standard Deviation 1420

SECONDARY outcome

Timeframe: 10 minutes, 4 hours, and 3, 5, 8, 10, and 30 days postdose

Population: Pharmacokinetic analysis set with available T1/2,z data

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.

Outcome measures

Measure	Etelcalcetide n=7 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Terminal Half-life (T1/2,z) of Etelcalcetide	5.77 days Standard Deviation 2.66

SECONDARY outcome

Timeframe: Baseline and day 30

Population: Treated participants

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.

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Number of Participants Who Developed Anti-etelcalcetide Binding Antibodies	2 Participants

SECONDARY outcome

Timeframe: 30 days

Population: All Treated participants

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.

Outcome measures

Measure	Etelcalcetide n=11 Participants Participants received a single, intravenous (IV) bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Number of Participants With Treatment-emergent Adverse Events Any adverse event	6 Participants
Number of Participants With Treatment-emergent Adverse Events Adverse events ≥ grade 3	2 Participants
Number of Participants With Treatment-emergent Adverse Events Adverse events ≥ grade 4	0 Participants
Number of Participants With Treatment-emergent Adverse Events Serious adverse events	0 Participants
Number of Participants With Treatment-emergent Adverse Events AEs leading to discontinuation of etelcalcetide	0 Participants
Number of Participants With Treatment-emergent Adverse Events Fatal adverse events	0 Participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related adverse events	0 Participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related AEs ≥ grade 3	0 Participants

Adverse Events

Etelcalcetide

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Etelcalcetide n=11 participants at risk Participants received a single, intravenous bolus administration of 0.035 mg/kg etelcalcetide at the end of hemodialysis on study day 1.
Gastrointestinal disorders Nausea	9.1% 1/11 • 30 days Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	9.1% 1/11 • 30 days Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Calcium ionised decreased	18.2% 2/11 • 30 days Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dizziness	9.1% 1/11 • 30 days Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	18.2% 2/11 • 30 days Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Paraesthesia	9.1% 1/11 • 30 days Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Surgical and medical procedures Catheter placement	9.1% 1/11 • 30 days Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Surgical and medical procedures Gastrostomy	9.1% 1/11 • 30 days Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	18.2% 2/11 • 30 days Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: medinfo@amgen.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER