Secondary Hyperparathyroidism in Patients With ESRD on HemodialysisPhase 1NCT02054572

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

A Phase 1 study testing [¹⁴C]Etelcalcetide in people with Secondary Hyperparathyroidism in Patients With ESRD on Hemodialysis, run by Amgen at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The primary objectives of this study were to determine the rate, extent, and routes of radioactivity excretion of [¹⁴C]etelcalcetide in feces, dialysate, and urine over time and to measure radioactivity concentrations in whole blood and plasma over time. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Secondary Hyperparathyroidism in Patients With ESRD on Hemodialysis
What is being tested?: [¹⁴C]Etelcalcetide
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 6 participants
Where: 1 siteUnited States
Study dates: 7 Feb 2014to 15 Aug 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
Male or female subject ≥ 18 years of age at the time of screening, with end stage renal disease receiving hemodialysis;
Body mass index is between 18 and 38 kg/m², inclusive;
Corrected calcium (calculated) level is > 8.3 mg/dL and intact parathyroid hormone (PTH) level is between 300 - 1200, inclusive; all other laboratory tests within clinically acceptable range to the investigator and sponsor at screening;
Female subjects must be of non-reproductive potential (ie, postmenopausal by history - no menses for 1 year and follicle-stimulating hormone (FSH) level consistent with postmenopausal status; OR history of hysterectomy; OR history of bilateral tubal ligation);
Negative screen for potential drugs of abuse at screening, unless positive result is expected based on approved concomitant medications;

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Negative alcohol test at screening;
Subject has functioning permanent dialysis access via fistula, hemodialysis (HD) catheter, or arteriovenous (AV) graft;
Subject must be receiving hemodialysis 3 times weekly for at least 1 year prior to day -1 (or is confirmed to be anuric based on historical and clinical assessment if on hemodialysis for less than one year), and have adequate hemodialysis with a delivered Kt/V ≥ 1.2 or urea reduction ratio (URR) ≥ 65% within 4 weeks to screening. The subject's routine hemodialysis session must be of 3-4.5 hours in duration, inclusive;
Subject has stable dialysis prescription and this prescription is not anticipated to change significantly during the course of the study.

Who cannot join

Female subjects who are lactating/breastfeeding or who plan to breastfeed while on study through 3 months after receiving the dose of study drug;
Females with a positive pregnancy test at screening;
Positive for human immunodeficiency virus (HIV) at screening or known diagnosis of acquired immune deficiency syndrome (AIDS);
Positive Hepatitis B Surface Antigen (HepBsAg) at screening (indicative of chronic Hepatitis B);
Positive for Hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR) at screening (indicative of active hepatitis C - screening is generally done by hepatitis C antibody (HepCAb), followed by hepatitis C virus RNA by PCR if HepCAb is positive);
Previous administration of AMG 416;

Show all 29Show fewer

Previous administration of any [¹⁴C] labeled drug substance within 1 year before study drug administration;
Subject has received cinacalcet within the 30 days prior to study drug administration (treatment with cinacalcet is prohibited during the study);
Subject has known sensitivity to any of the products or components to be administered during dosing;
Use of concomitant medication other than that used in the management of end stage renal disease and its expected comorbidities that could in the opinion of the investigator or Amgen medical monitor interfere with the safety of subjects or interpretation of study results;
Known illicit drug abuse within 12 months of day -1;
Unwilling or unable to limit alcohol consumption throughout the course of the study;
Alcohol is limited to no more than 2 units per day during the outpatient period of the study through completion of day 39. A standard unit is equivalent to 12 ounces of regular beer, 8-9 ounces of malt liquor, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits;
Receiving or has received any investigational drug (or is currently using an investigational device) within the 30 days before receiving study drug, or at least 10 times the respective elimination half-life (whichever is longer);
Subject has lost 500 mL or more of blood or plasma within 8 weeks of study drug administration or during the study period;
Subjects with hemodynamic instability during hemodialysis;
Anticipated or scheduled kidney transplant during the study period
Subject has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator;
Subject has an active infection at screening or day -1, or a history of any illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject;
History of malignancy (within 5 years before day -1) of any type, other than surgically excised non-melanomatous skin cancers;
Subject's 12-lead electrocardiogram (ECG) at screening suggests unstable arrhythmia or other cardiac abnormality that could place the subject at increased risk, based upon the Investigator's opinion
Subject has poorly controlled hypertension;
Subject has a history of symptomatic ventricular dysrhythmias or Torsades de Pointes;
Subject has a history within the past 6 months of angina pectoris with symptoms that occur at rest or minimal activity or a history of congestive heart failure (New York Heart Association Classification III or IV);
Subject has a history of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 6 months prior to screening;
Subject is receiving treatment for a seizure disorder or has a history of a seizure within the last 12 months prior to screening;
Subject has had major surgery (excluding minor surgery and hemodialysis access repair) within the last 8 weeks prior to screening;
Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and Investigator's knowledge;
History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

Trial locations and contacts

1 site in 1 country.

United States1 site

DaVita Clinical Research Center
Minneapolis, Minnesota, 55404

Other trials in United States

About this study

Official title: An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Biotransformation and Excretion of [¹⁴C]AMG 416 in Patients With End Stage Renal Disease Receiving Dialysis

Read the detailed description

Six adult male or female patients with end stage renal disease requiring hemodialysis will be enrolled to receive 750 nCi of [¹⁴C]-labeled etelcalcetide formulated in 10 mg etelcalcetide administered as a single 2 mL intravenous dose at the end of hemodialysis.

Participants will spend the first approximately 12 days in confinement at the clinic (day -1 until completion of day 11 study procedures). Blood samples, and complete collections of dialysate, dialysis membrane (as necessary), urine (as available), and feces will be analyzed for radioactivity content by accelerator mass spectrometry (AMS). Following the confinement period, participants will return to the site on an outpatient basis in accordance to their routine dialysis sessions up to day 39. Blood and dialysate samples and dialysis membranes will be collected at specified times during the outpatient visit period.

Participants may be asked to return so the site for the Extended Pharmacokinetic Collection Period. During the Extended Pharmacokinetic Collection Period, participants will return to the site for 3 consecutive hemodialysis sessions (Collection Period 1) and then again approximately one month later, for an additional 3 consecutive hemodialysis sessions (Collection Period 2).

Conditions: Secondary Hyperparathyroidism in Patients With ESRD on Hemodialysis
Being tested: [¹⁴C]Etelcalcetide
Keywords: AMG 416, ESRD, hemodialysis
Medical subject headings: Kidney Failure, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

[¹⁴C]EtelcalcetideDrug
Also called AMG 416, Parsabiv™
750 nCi of [¹⁴C]etelcalcetide formulated as a single 10 mg dose of etelcaletide in 2 mL liquid solution for bolus intravenous (IV) administration at the end of hemodialysis.

Study groups in NCT02054572
Study group	Role	What they receive
[¹⁴C]Etelcalcetide	Experimental	Participants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1. Receives: Drug: [¹⁴C]Etelcalcetide

What is being measured

The primary outcome is the main question the study is designed to answer.

Cumulative Excretion of Radioactivity
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.
Measured: Day 1 to day 176
Time to Maximum Observed Concentration (Tmax) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Total radioactive counts in plasma was determined by accelerator mass spectrometry (AMS).
Measured: 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.
Maximum Observed Concentration (Cmax) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Measured: 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.
Time to Last Observed Plasma Concentration of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Measured: 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.
Last Observed Plasma Concentration (Clast) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Measured: 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.
Apparent Terminal Half-life (T½) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Measured: 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.
Area Under the Curve From Time Zero to 3 Days Post-dose (AUC3d) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Measured: 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.
Area Under the Curve From Time Zero to 10 Days Post-dose (AUC10d) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Measured: 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.
Area Under the Arterial Plasma Concentration-time Curve Obtained During Hemodialysis on Day 4 for Etelcalcetide
Etelcalcetide plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Measured: 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.
Area Under the Venous Plasma Concentration-time Curve Obtained During Hemodialysis on Day 4 for Etelcalcetide
Etelcalcetide plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Measured: 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.

Secondary outcomes (10)

Time to Maximum Observed Concentration (Tmax) of Etelcalcetide
Etelcalcetide plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Measured: 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.
Maximum Observed Concentration (Cmax) of Etelcalcetide
Measured: 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.
Time to Last Observed Plasma Concentration of Etelcalcetide
Measured: 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.
Last Observed Plasma Concentration (Clast) of Etelcalcetide
Measured: 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.
Area Under the Curve From Time Zero to 3 Days Post-dose (AUC3d) of Etelcalcetide
Measured: 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.
Area Under the Curve From Time Zero to 10 Days Post-dose (AUC10d) of Etelcalcetide
Measured: 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.
Hemodialysis Clearance of Etelcalcetide During Hemodialysis on Day 4
Measured: 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.
Hemodialysis Extraction Ratio for Etelcalcetide During Hemodialysis on Day 4
Measured: 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.
Number of Participants With Adverse Events
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.
Measured: From first dose of etelcalcetide to day 39
Number of Participants With Anti-etelcalcetide Antibodies
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).
Measured: Day -1 and day 39

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Feb 201415 Aug 2014

First posted4 Feb 2014 (estimated)
Study start7 Feb 2014
Primary completion15 Apr 2014
Study completion15 Aug 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Secondary Hyperparathyroidism in Patients With ESRD on HemodialysisStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 6 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02054572
Sponsor's protocol ID: 20130147
Status last verified: Aug 2018
First submitted: 3 Feb 2014
Last updated: 31 Aug 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Wu L, Melhem M, Subramanian R, Wu B. Drug disposition model of radiolabeled etelcalcetide in patients with chronic kidney disease and secondary hyperparathyroidism on hemodialysis. J Pharmacokinet Pharmacodyn. 2017 Feb;44(1):43-53. doi: 10.1007/s10928-016-9503-z. Epub 2017 Jan 6.
PubMed 28063122
Wu B, Melhem M, Subramanian R, Chen P, Jaramilla Sloey B, Fouqueray B, Hock MB, Skiles GL, Chow AT, Lee E. Clinical Pharmacokinetics and Pharmacodynamics of Etelcalcetide, a Novel Calcimimetic for Treatment of Secondary Hyperparathyroidism in Patients With Chronic Kidney Disease on Hemodialysis. J Clin Pharmacol. 2018 Jun;58(6):717-726. doi: 10.1002/jcph.1090. Epub 2018 Mar 13.
PubMed 29534286

Study at a glance

From the registry record, last updated by the sponsor on 31 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Biotransformation and Excretion of [¹⁴C]AMG 416 in Patients With End Stage Renal Disease Receiving Dialysis
ClinicalTrials.gov ID: NCT02054572
Acronym / sponsor ID: 20130147
Conditions: Secondary Hyperparathyroidism in Patients With ESRD on Hemodialysis
Keywords: AMG 416, ESRD, hemodialysis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 6 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 7 Feb 2014 (actual)
Primary completion: 15 Apr 2014 (actual)
Study completion: 15 Aug 2014 (actual)
First posted: 4 Feb 2014 (estimated)
Results: Posted 14 Apr 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
[¹⁴C]Etelcalcetide	Experimental	Drug: [¹⁴C]EtelcalcetideParticipants received a single dose of 10 mg radiolabelled etelcalcetide administered by intravenous (IV) bolus injection at the end of hemodialysis on day 1.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
Male or female subject ≥ 18 years of age at the time of screening, with end stage renal disease receiving hemodialysis;
Body mass index is between 18 and 38 kg/m², inclusive;
Corrected calcium (calculated) level is > 8.3 mg/dL and intact parathyroid hormone (PTH) level is between 300 - 1200, inclusive; all other laboratory tests within clinically acceptable range to the investigator and sponsor at screening;
Female subjects must be of non-reproductive potential (ie, postmenopausal by history - no menses for 1 year and follicle-stimulating hormone (FSH) level consistent with postmenopausal status; OR history of hysterectomy; OR history of bilateral tubal ligation);

Key exclusion criteria (29 listed)

Female subjects who are lactating/breastfeeding or who plan to breastfeed while on study through 3 months after receiving the dose of study drug;
Females with a positive pregnancy test at screening;
Positive for human immunodeficiency virus (HIV) at screening or known diagnosis of acquired immune deficiency syndrome (AIDS);
Positive Hepatitis B Surface Antigen (HepBsAg) at screening (indicative of chronic Hepatitis B);
Positive for Hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR) at screening (indicative of active hepatitis C - screening is generally done by hepatitis C antibody (HepCAb), followed by hepatitis C virus RNA by PCR if HepCAb is positive);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
[¹⁴C]EtelcalcetideAlso: AMG 416, Parsabiv™750 nCi of [¹⁴C]etelcalcetide formulated as a single 10 mg dose of etelcaletide in 2 mL liquid solution for bolus intravenous (IV) administration at the end of hemodialysis.	Drug	[¹⁴C]Etelcalcetide

Primary outcome

Cumulative Excretion of Radioactivity
Time frame: Day 1 to day 176
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.
Time to Maximum Observed Concentration (Tmax) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Time frame: 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.
Total radioactive counts in plasma was determined by accelerator mass spectrometry (AMS).
Maximum Observed Concentration (Cmax) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Time frame: 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.
Time to Last Observed Plasma Concentration of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Time frame: 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.
Last Observed Plasma Concentration (Clast) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Time frame: 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.
Apparent Terminal Half-life (T½) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Time frame: 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.
Area Under the Curve From Time Zero to 3 Days Post-dose (AUC3d) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Time frame: 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.
Area Under the Curve From Time Zero to 10 Days Post-dose (AUC10d) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma
Time frame: 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.
Area Under the Arterial Plasma Concentration-time Curve Obtained During Hemodialysis on Day 4 for Etelcalcetide
Time frame: 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.
Etelcalcetide plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Area Under the Venous Plasma Concentration-time Curve Obtained During Hemodialysis on Day 4 for Etelcalcetide
Time frame: 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.
Etelcalcetide plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

10 secondary outcomes

Time to Maximum Observed Concentration (Tmax) of Etelcalcetide
Time frame: 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.
Maximum Observed Concentration (Cmax) of Etelcalcetide
Time frame: 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.
Time to Last Observed Plasma Concentration of Etelcalcetide
Time frame: 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.
Last Observed Plasma Concentration (Clast) of Etelcalcetide
Time frame: 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.
Area Under the Curve From Time Zero to 3 Days Post-dose (AUC3d) of Etelcalcetide
Time frame: 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.
Area Under the Curve From Time Zero to 10 Days Post-dose (AUC10d) of Etelcalcetide
Time frame: 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.
Hemodialysis Clearance of Etelcalcetide During Hemodialysis on Day 4
Time frame: 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.
Hemodialysis Extraction Ratio for Etelcalcetide During Hemodialysis on Day 4
Time frame: 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.
Number of Participants With Adverse Events
Time frame: From first dose of etelcalcetide to day 39
Number of Participants With Anti-etelcalcetide Antibodies
Time frame: Day -1 and day 39

Results and safety

Results posted to the registry on 14 Apr 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
[¹⁴C]Etelcalcetide	6	6

Primary outcome: Cumulative Excretion of Radioactivity

Time frame: Day 1 to day 176. Mean (Standard Deviation). Unit: Percentage of administered dose

Measure	[¹⁴C]Etelcalcetide n = 4
Dialysate (Measured)	35.29 (4.17)
Dialysate (Estimated)	24.26 (2.71)
Urine (Measured)	0.75 (1.13)
Urine (Estimated)	2.40 (3.79)
Feces (Measured)	1.17 (0.13)
Feces (Estimated)	3.34 (0.57)
Total	67.19 (1.37)

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

Primary outcome: Time to Maximum Observed Concentration (Tmax) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma

Time frame: 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.. Median (Full Range). Unit: minutes

Measure	[¹⁴C]Etelcalcetide n = 6
Value	10 (10 to 12)

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

Primary outcome: Maximum Observed Concentration (Cmax) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma

Measure	[¹⁴C]Etelcalcetide n = 6
Value	697 (207)

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

Primary outcome: Time to Last Observed Plasma Concentration of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma

Measure	[¹⁴C]Etelcalcetide n = 6
Value	164 (37.6 to 174)

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

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of etelcalcetide to day 39.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
[¹⁴C]Etelcalcetide	1 of 6 (16.7%)	5 of 6 (83.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 28063122Wu L, Melhem M, Subramanian R, Wu B. Drug disposition model of radiolabeled etelcalcetide in patients with chronic kidney disease and secondary hyperparathyroidism on hemodialysis. J Pharmacokinet Pharmacodyn. 2017 Feb;44(1):43-53. doi: 10.1007/s10928-016-9503-z. Epub 2017 Jan 6.
Background: PubMed 29534286Wu B, Melhem M, Subramanian R, Chen P, Jaramilla Sloey B, Fouqueray B, Hock MB, Skiles GL, Chow AT, Lee E. Clinical Pharmacokinetics and Pharmacodynamics of Etelcalcetide, a Novel Calcimimetic for Treatment of Secondary Hyperparathyroidism in Patients With Chronic Kidney Disease on Hemodialysis. J Clin Pharmacol. 2018 Jun;58(6):717-726. doi: 10.1002/jcph.1090. Epub 2018 Mar 13.
AmgenTrials clinical trials websiteLink provided by the sponsor.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing [¹⁴C]Etelcalcetide in people with Secondary Hyperparathyroidism in Patients With ESRD on Hemodialysis, run by Amgen at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cumulative Excretion of Radioactivity (time frame: Day 1 to day 176). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02054572, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2018.