One-year safety and efficacy of intravenous etelcalcetide in patients on hemodialysis with secondary hyperparathyroidism

Abstract

Background: Secondary hyperparathyroidism (sHPT), a common complication of chronic kidney disease, is characterized by elevated serum parathyroid hormone (PTH). Etelcalcetide is an intravenous calcimimetic that increases sensitivity of the calcium-sensing receptor to calcium and decreases PTH secretion. This open-label extension (OLE) trial evaluated the long-term effects of etelcalcetide for sHPT treatment in patients receiving hemodialysis.

Methods: This 52-week, multicenter, single-arm OLE enrolled patients from three parent trials: two randomized, double-blind, placebo-controlled trials and one open-label, single-arm, 'switch' study from cinacalcet to etelcalcetide. The primary endpoint was to investigate the nature, frequency, severity and relation to treatment of all adverse events (AEs) reported throughout the trial. Secondary endpoints included the proportion of patients with >30% reduction from baseline in PTH and the percentage change from baseline in PTH, albumin-corrected calcium (Ca), phosphate (P) and the calcium-phosphate product (Ca × P).ClinicalTrials.gov identifier: NCT01785875; Amgen study: 20120231.

Results: Overall, 89.8% of the patients experienced one or more treatment-emergent AE. The most common were decreased blood Ca (43.3%), diarrhea (10.8%), vomiting (10.4%) and nausea (9.6%); symptomatic hypocalcemia occurred in 3.7% of the patients. Approximately 68% of patients achieved >30% reduction in PTH, and ∼56% achieved PTH ≤300 pg/mL. Mean percent changes from baseline ranged from -25.4% to -26.1% for PTH, -8.3% to -9.1% for Ca, -3.6% to -4.1% for P and -12.0% to -12.6% for Ca × P.

Conclusions: Etelcalcetide effectively lowered PTH and its effect was sustained, while no new safety concerns emerged over a 1-year treatment period.

Keywords: chronic kidney disease; etelcalcetide; open-label extension; safety, secondary hyperparathyroidism.

FIGURE 1

Patient disposition. ^aTwo of the trials were randomized, double-blind, placebo-controlled trials conducted in 1023 patients [22]; the other trial was an open-label, single-arm, ‘switch’ from cinacalcet to etelcalcetide in 158 patients [23]. ^bSixteen patients from one site withdrew consent on 20 or 21 November 2014, subsequent to the investigator’s decisions to withdraw from the trial. Additionally, three patients from the same site had missing end-of-study data.

FIGURE 2

Proportion of patients receiving each dose level of etelcalcetide (mg/session) at selected visits. ^aOne patient received 17.5 mg of etelcalcetide in Week 26, although the maximum dose per protocol was 15 mg.

FIGURE 3

Proportion of patients with low Ca values during the trial for the current OLE study (black) versus the active treatment arm of the placebo-controlled trials [22] (gray). Ca, albumin-corrected calcium.

FIGURE 4

Mean (SE) predialysis PTH (A), Ca (B) and P (C) concentrations over time. BL, baseline; Ca, albumin-corrected calcium; P, phosphate.

FIGURE 5

Concomitant medication use.