Phase 1
N=6
Pharmacokinetics and Excretion of [¹⁴C]Etelcalcetide (AMG 416) in Patients With End Stage Renal Disease (ESRD) Receiving Dialysis
Secondary Hyperparathyroidism in Patients With ESRD on Hemodialysis
Bottom Line
View on ClinicalTrials.gov: NCT02054572 ↗Enrolled (actual)
6
Serious AEs
16.7%
Results posted
Apr 2017
Primary outcome: Primary: Cumulative Excretion of Radioactivity — 35.29; 24.26; 0.75; 2.40 Percentage of administered dose
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- [¹⁴C]Etelcalcetide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Amgen
- Primary completion
- Apr 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cumulative Excretion of Radioactivity |
35.29; 24.26; 0.75; 2.40; 1.17; 3.34 | — |
| PRIMARY Time to Maximum Observed Concentration (Tmax) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma |
10 | — |
| PRIMARY Maximum Observed Concentration (Cmax) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma |
697 | — |
| PRIMARY Time to Last Observed Plasma Concentration of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma |
164 | — |
| PRIMARY Last Observed Plasma Concentration (Clast) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma |
3.01 | — |
| PRIMARY Apparent Terminal Half-life (T½) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma |
35.9 | — |
| PRIMARY Area Under the Curve From Time Zero to 3 Days Post-dose (AUC3d) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma |
585 | — |
| PRIMARY Area Under the Curve From Time Zero to 10 Days Post-dose (AUC10d) of [¹⁴C]Etelcalcetide-derived Radioactivity in Plasma |
1220 | — |
| PRIMARY Area Under the Arterial Plasma Concentration-time Curve Obtained During Hemodialysis on Day 4 for Etelcalcetide |
1.79 | — |
| PRIMARY Area Under the Venous Plasma Concentration-time Curve Obtained During Hemodialysis on Day 4 for Etelcalcetide |
1.09 | — |
| SECONDARY Time to Maximum Observed Concentration (Tmax) of Etelcalcetide |
10 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of Etelcalcetide |
347 | — |
| SECONDARY Time to Last Observed Plasma Concentration of Etelcalcetide |
37.8 | — |
| SECONDARY Last Observed Plasma Concentration (Clast) of Etelcalcetide |
2.50 | — |
| SECONDARY Area Under the Curve From Time Zero to 3 Days Post-dose (AUC3d) of Etelcalcetide |
81.6 | — |
| SECONDARY Area Under the Curve From Time Zero to 10 Days Post-dose (AUC10d) of Etelcalcetide |
160 | — |
| SECONDARY Hemodialysis Clearance of Etelcalcetide During Hemodialysis on Day 4 |
7660 | — |
| SECONDARY Hemodialysis Extraction Ratio for Etelcalcetide During Hemodialysis on Day 4 |
0.385 | — |
| SECONDARY Number of Participants With Adverse Events |
5; 1; 0; 0; 2; 0 | — |
| SECONDARY Number of Participants With Anti-etelcalcetide Antibodies |
0; 0 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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;
- 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.
Exclusion Criteria
- 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;
- 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
Data sourced from ClinicalTrials.gov (NCT02054572). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.