Pharmacokinetics and Excretion of [¹⁴C]Etelcalcetide (AMG 416) in Patients With End Stage Renal Disease (ESRD) Receiving Dialysis
Condition: Secondary Hyperparathyroidism in Patients With ESRD on Hemodialysis
MeSH terms: Kidney Failure, Chronic; Hyperparathyroidism; Hyperparathyroidism, Secondary
Intervention: [¹⁴C]Etelcalcetide
Intervention description: 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.
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: AMG 416, ESRD, hemodialysis

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 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.