Safety, Tolerability and Pharmacokinetics of Etelcalcetide in Hemodialysis Patients With Secondary Hyperparathyroidism

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety and tolerability of single rising doses of etelcalcetide in hemodialysis patients with secondary hyperparathyroidism.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety and Tolerability of Single Ascending Doses of KAI-4169 in Hemodialysis Subjects With Secondary Hyperparathyroidism

Conditions
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Hyperparathyroidism, Secondary

Intervention / Treatment
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* Drug: Placebo
* Drug: Etelcalcetide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects provides written informed consent. Intact parathyroid hormone (iPTH) ≥ 400 pg/mL (≥ 300 and < 1200 pg/ml for Cohorts 1-3). Serum corrected calcium ≥ 9.0 mg/dL Receiving hemodialysis three times per week for at least 3 months and had adequate hemodialysis with a delivered Kt/V (dialyzer clearance of urea * dialysis time/ volume of distribution of urea) ≥ 1.2 or urea reduction ratio (URR) ≥ 65%. Excepting chronic renal failure, subject is judged to be in stable medical condition based on medical history, physical examination, and routine laboratory tests Exclusion Criteria: History or symptomatic ventricular dysrhythmias History of angina pectoris or congestive heart failure History of myocardial infarction, coronary angioplasty, or coronary artery bypass grafting within the past 6 months History of or treatment for seizure disorder Recent (3 months) parathyroidectomy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received a single dose of placebo intravenous (IV) injection after hemodialysis. | Drug: Placebo<br>* Single IV injection.<br>|
| Experimental: Etelcalcetide<br>Participants received a single dose of etelcalcetide by intravenous (IV) injection after hemodialysis. | Drug: Etelcalcetide<br>* Single IV injection. The initial dose was 5 mg and dose escalation proceeded with subsequent doses of 10 mg, 20 mg, 40 mg and 60 mg.<br>* Other names: AMG 416;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events |  | For Cohorts 1 to 3, from administration of study drug up until 21 days after study drug administration; for Cohorts 4 and 5 from administration of study drug until 28 days after study drug administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Serum Parathyroid Hormone (PTH) |  | Baseline and 30 minutes, 1, 4, 8, 18, 24, 32, 42, 48, and 56 hours post-dose, day 4 (discharge) and for Cohorts 4 and 5 only, days 8, 15 and 29 | 
| Percent Change From Baseline in Serum Corrected Calcium |  | Baseline and 30 minutes, 1, 4, 8, 18, 24, 32, 42, 48, and 56 hours post-dose, day 4 (discharge) and for Cohorts 4 and 5 only, days 8, 15 and 29 | 
| Percent Change From Baseline in Ionized Calcium |  | Baseline and 30 minutes, 1, 4, 8, 18, 24, 32, 42, 48, and 56 hours post-dose, and day 4 (discharge). | 
| Percent Change From Baseline in Serum Phosphorus |  | Baseline and 30 minutes, 1, 4, 8, 18, 24, 32, 42, 48, and 56 hours post-dose, and day 4 (discharge). | 
| Percent Change From Baseline in Calcium Phosphorus Product |  | Baseline and 30 minutes, 1, 4, 8, 18, 24, 32, 42, 48, and 56 hours post-dose, and day 4 (discharge). | 
| Maximum Observed Plasma Concentration (Cmax) of Etelcalcetide |  | Pre-dose and at 0.17, 0.5, 1, 4, 8, 18, 24, 32, and 48 hours after study drug administration and prior to discharge from the clinical research unit ( 65 hours). | 
| Area Under the Concentration-time Curve From Time 0 to 65 Hours Post-dose for Etelcalcetide |  | Pre-dose and at 0.17, 0.5, 1, 4, 8, 18, 24, 32, and 48 hours after study drug administration and prior to discharge from the clinical research unit ( 65 hours). | 
| Observed Area Under the Concentration-time Curve Extrapolated to Infinity (AUCINFobs) for Etelcalcetide |  | Pre-dose and at 0.17, 0.5, 1, 4, 8, 18, 24, 32, and 48 hours after study drug administration and prior to discharge from the clinical research unit ( 65 hours). | 
| Percent AUC Extrapolated to Infinity (AUCINF) Resulting From Extrapolation From 65 Hours Onward for Etelcalcetide |  | Pre-dose and at 0.17, 0.5, 1, 4, 8, 18, 24, 32, and 48 hours after study drug administration and prior to discharge from the clinical research unit ( 65 hours). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Trial, Phase 1, Renal Dialysis, Secondary Hyperparathyroidism, Parathyroid hormone