Trial Outcomes & Findings for Pharmacokinetics and Excretion of [¹⁴C]Etelcalcetide (AMG 416) in Patients With End Stage Renal Disease (ESRD) Receiving Dialysis (NCT NCT02054572)

NCT ID: NCT02054572

Last Updated: 2018-08-31

Results Overview

The total radioactivity in excreta (urine and feces) or dialysate and dialysis membrane is expressed as a percentage of the total radioactive \[¹⁴C\] administered (dose). Total radioactive counts in dialysate, dialyzer, feces, and urine were determined by accelerator mass spectrometry (AMS). Radioactivity excreted during non-sampled days was estimated by interpolation and extrapolation of the measured data.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 6 participants
• Primary outcome timeframe: Day 1 to day 176
• Results posted on: 2018-08-31

Participant Flow

This study was conducted at a single center in the United States from 07 February 2014 to 15 August 2014.

Participant milestones

Measure	[¹⁴C]Etelcalcetide Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics and Excretion of [¹⁴C]Etelcalcetide (AMG 416) in Patients With End Stage Renal Disease (ESRD) Receiving Dialysis

Baseline characteristics by cohort

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Age, Continuous	56.3 years STANDARD_DEVIATION 16.4 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants
Race/Ethnicity, Customized Black (or African American)	5 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants
Race/Ethnicity, Customized White	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to day 176

Population: Participants who received any amount of \[¹⁴C\]etelcalcetide with available excretion data

The total radioactivity in excreta (urine and feces) or dialysate and dialysis membrane is expressed as a percentage of the total radioactive [¹⁴C] administered (dose). Total radioactive counts in dialysate, dialyzer, feces, and urine were determined by accelerator mass spectrometry (AMS). Radioactivity excreted during non-sampled days was estimated by interpolation and extrapolation of the measured data.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=4 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Cumulative Excretion of Radioactivity Dialysate (Measured)	35.29 Percentage of administered dose Standard Deviation 4.17
Cumulative Excretion of Radioactivity Dialysate (Estimated)	24.26 Percentage of administered dose Standard Deviation 2.71
Cumulative Excretion of Radioactivity Urine (Measured)	0.75 Percentage of administered dose Standard Deviation 1.13
Cumulative Excretion of Radioactivity Urine (Estimated)	2.40 Percentage of administered dose Standard Deviation 3.79
Cumulative Excretion of Radioactivity Feces (Measured)	1.17 Percentage of administered dose Standard Deviation 0.13
Cumulative Excretion of Radioactivity Feces (Estimated)	3.34 Percentage of administered dose Standard Deviation 0.57
Cumulative Excretion of Radioactivity Total	67.19 Percentage of administered dose Standard Deviation 1.37

PRIMARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Total radioactive counts in plasma was determined by accelerator mass spectrometry (AMS).

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Time to Maximum Observed Concentration (Tmax) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma	10 minutes Interval 10.0 to 12.0

PRIMARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Maximum Observed Concentration (Cmax) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma	697 ng-eq/mL Standard Deviation 207 • Interval 10.0 to 12.0

PRIMARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Time to Last Observed Plasma Concentration of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma	164 days Interval 37.6 to 174.0

PRIMARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Last Observed Plasma Concentration (Clast) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma	3.01 ng-eq/mL Interval 2.06 to 24.7

PRIMARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Apparent Terminal Half-life (T½) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma	35.9 days Standard Deviation 2.99 • Interval 10.0 to 12.0

PRIMARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Area Under the Curve From Time Zero to 3 Days Post-dose (AUC3d) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma	585 day*ng-eq/mL Standard Deviation 98.8 • Interval 10.0 to 12.0

PRIMARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Area Under the Curve From Time Zero to 10 Days Post-dose (AUC10d) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma	1220 day*ng-eq/mL Standard Deviation 172 • Interval 10.0 to 12.0

PRIMARY outcome

Timeframe: Day 4 within 10 minutes after the start of hemodialysis, at 2 hours after the start of hemodialysis, and within 10 minutes before the end of hemodialysis.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Etelcalcetide plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Area Under the Arterial Plasma Concentration-time Curve Obtained During Hemodialysis on Day 4 for Etelcalcetide	1.79 ng*day/mL Standard Deviation 0.467 • Interval 10.0 to 12.0

PRIMARY outcome

Timeframe: Day 4 within 10 minutes after the start of hemodialysis, at 2 hours after the start of hemodialysis, and within 10 minutes before the end of hemodialysis.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Etelcalcetide plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Area Under the Venous Plasma Concentration-time Curve Obtained During Hemodialysis on Day 4 for Etelcalcetide	1.09 ng*day/mL Standard Deviation 0.264 • Interval 10.0 to 12.0

SECONDARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Etelcalcetide plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Time to Maximum Observed Concentration (Tmax) of Etelcalcetide	10 minutes Interval 10.0 to 11.0

SECONDARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Maximum Observed Concentration (Cmax) of Etelcalcetide	347 ng/mL Standard Deviation 69.5 • Interval 10.0 to 12.0

SECONDARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Time to Last Observed Plasma Concentration of Etelcalcetide	37.8 days Interval 37.6 to 145.0

SECONDARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Last Observed Plasma Concentration (Clast) of Etelcalcetide	2.50 ng/mL Interval 0.21 to 2.8

SECONDARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Area Under the Curve From Time Zero to 3 Days Post-dose (AUC3d) of Etelcalcetide	81.6 day*ng/mL Standard Deviation 8.41 • Interval 10.0 to 12.0

SECONDARY outcome

Timeframe: Samples were collected from pre-dose on day 1 to day 39; additional samples were collected at 3 consecutive hemodialysis sessions from days 129 -148 and approximately 1 month later at an additional 3 consecutive hemodialysis sessions from days 157-176.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Area Under the Curve From Time Zero to 10 Days Post-dose (AUC10d) of Etelcalcetide	160 day*ng/mL Standard Deviation 16.9 • Interval 10.0 to 12.0

SECONDARY outcome

Timeframe: Day 4 within 10 minutes after the start of hemodialysis, at 2 hours after the start of hemodialysis, and within 10 minutes before the end of hemodialysis.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Hemodialysis Clearance of Etelcalcetide During Hemodialysis on Day 4	7660 mL/hr Standard Deviation 1380

SECONDARY outcome

Timeframe: Day 4 within 10 minutes after the start of hemodialysis, at 2 hours after the start of hemodialysis, and within 10 minutes before the end of hemodialysis.

Population: Participants who received any part of the \[¹⁴C\]etelcalcetide dose and had measurable concentrations in at least 1 sample were included in the analysis.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Hemodialysis Extraction Ratio for Etelcalcetide During Hemodialysis on Day 4	0.385 ratio Standard Deviation 0.0679

SECONDARY outcome

Timeframe: From first dose of etelcalcetide to day 39

Population: Participants who received any amount of \[¹⁴C\]etalcalcetide

A treatment-related adverse event (TRAE) is any adverse event (AE) that per investigator review has a reasonable possibility of being caused by the investigational product.

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Number of Participants With Adverse Events Any adverse event (AE)	5 participants
Number of Participants With Adverse Events Serious adverse events	1 participants
Number of Participants With Adverse Events AE leading to discontinuation of etelcalcetide	0 participants
Number of Participants With Adverse Events Fatal adverse events	0 participants
Number of Participants With Adverse Events Treatment-related adverse events (TRAEs)	2 participants
Number of Participants With Adverse Events Treatment-related serious adverse events	0 participants
Number of Participants With Adverse Events TRAE leading to discontinuation of etelcalcetide	0 participants
Number of Participants With Adverse Events Fatal treatment-related adverse events	0 participants

SECONDARY outcome

Timeframe: Day -1 and day 39

Population: Participants who received any amount of \[¹⁴C\]etalcalcetide

The presence of anti-etelcalcetide antibodies was assessed and confirmed using a dual-flow cell biosensor immunoassay at baseline (day -1) and at the end of study visit (day 39).

Outcome measures

Measure	[¹⁴C]Etelcalcetide n=6 Participants Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.
Number of Participants With Anti-etelcalcetide Antibodies Pre-existing antibody incidence (Day -1)	0 participants
Number of Participants With Anti-etelcalcetide Antibodies Developing antibody incidence (Day 39)	0 participants

Adverse Events

[¹⁴C]Etelcalcetide

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	[¹⁴C]Etelcalcetide n=6 participants at risk Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by IV bolus at the end of hemodialysis on day 1.
Infections and infestations Pneumonia	16.7% 1/6 • From first dose of etelcalcetide to day 39. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Measure	[¹⁴C]Etelcalcetide n=6 participants at risk Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by IV bolus at the end of hemodialysis on day 1.
Gastrointestinal disorders Constipation	33.3% 2/6 • From first dose of etelcalcetide to day 39. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Flatulence	16.7% 1/6 • From first dose of etelcalcetide to day 39. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	16.7% 1/6 • From first dose of etelcalcetide to day 39. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	16.7% 1/6 • From first dose of etelcalcetide to day 39. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Upper respiratory tract infection	16.7% 1/6 • From first dose of etelcalcetide to day 39. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Dermatitis contact	16.7% 1/6 • From first dose of etelcalcetide to day 39. 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

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