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

Phase 1

Completed

• Conditions: Hyperparathyroidism, Secondary
• Interventions: Drug: Placebo; Drug: Etelcalcetide

• Registration Number: NCT01134562
• Lead Sponsor: KAI Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-05-28
• Study First Submitted QC: 2010-06-01
• Study First Posted: 2010-06-02
• Study Start: 2010-09-07
• Primary Completion: 2011-04-02
• Study Completion: 2011-04-02
• Results First Submitted: 2017-03-01
• Status Verified: 2017-05
• Results First Submitted QC: 2017-05-26
• Last Update Submitted: 2017-05-26
• Results First Posted: 2018-01-02
• Last Update Posted: 2018-01-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received a single dose of placebo intravenous (IV) injection after hemodialysis.
Etelcalcetide	Etelcalcetide	Participants received a single dose of etelcalcetide by intravenous (IV) injection after hemodialysis.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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).
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 Calcium Phosphorus Product	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 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).
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).
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).