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Introduction: The clinical trial on the Development of a treatment strategy for chronic kidney diseasemineral and bone disorder by a mUltilateral mechanism of ETelcalcetide hydrochloride, or the DUET trial, was designed to determine the efficacy of etelcalcetide, an intravenous calcimimetic, for control of secondary hyperparathyroidism (SHPT). Methods: Eligible SHPT maintenance hemodialysis patients (n ¼ 124) were randomized (1:1:1) for inclusion in the DUET trial, a 12-week, multicenter, open-label, parallel-group study (jRCTs041180108), and assigned to either an etelcalcetide þ active vitamin D group (group EþD), an etelcalcetide þ oral calcium preparation group (group EþCa), or a control group (group C). The primary endpoint was number of patients with a 50% reduction from baseline of intact parathyroid hormone (iPTH) levels, and iPTH levels # 240 pg/mL at 12 weeks after start of the trial. Results: The proportion of patients reaching the primary endpoint (95% confidence interval [CI]) was 90.0% (76.3%-97.2%) in group EþD, 56.8% (39.5%-72.9%) in group EþCa, and 19.5% (8.8%-34.9%) in group C. Etelcalcetide treatment led to a significant increase in the number of patients achieving the endpoint (odds ratio, 13.4; 95% CI, 5.10-35.3) on logistic regression analysis, with iPTH, corrected serum calcium, and phosphate at baseline as covariates. Significantly more patients achieved the endpoint in group EþD compared with group EþCa (odds ratio, 6.35; 95% CI, 1.79-22.48). There were fewer hypocalcemic visits in group EþD compared with group EþCa (P ¼ 0.018), yet the former group was prone to hyperphosphatemia. Conclusion: Etelcalcetide showed good control of iPTH for maintenance hemodialysis patients with SHPT. Active vitamin D was useful in correcting hypocalcemia, but the oral calcium preparation was superior for suppression of hyperphosphatemia.

Background: Secondary hyperparathyroidism (SHPT) is a common complication in advanced chronic kidney disease (CKD). The aims of this study are to clarify the efficacy of etelcalcetide, a novel-approved intravenous calcimimetic, for evaluating the optimal therapy for etelcalcetide-induced hypocalcemia, and to identify sensitive markers for vascular calcification in patients undergoing maintenance dialysis. Methods: The Development of treatment strategy for CKD-MBD by mUltilateral mechanism of ETelcalcetide hydrochloride (DUET) study is a 12-week multicenter, open-label, randomized (1:1:1), parallel-group study in SHPT patients undergoing maintenance hemodialysis. A total of 120 patients will be randomly assigned to etelcalcetide + active vitamin D, etelcalcetide + oral calcium preparation, or control (standard therapy) groups. If hypocalcemia is induced by etelcalcetide, active vitamin D and oral calcium preparations will be administered, in addition to the original medications, to patients allocated to etelcalcetide + active vitamin D and etelcalcetide + oral calcium preparation, respectively. The primary endpoint will be to compare the proportion of patients with a 50% reduction in serum intact parathyroid hormone (iPTH) levels after 12 treatment weeks with etelcalcetide relative to baseline values and iPTH levels ≤ 240 pg/mL at the 12-week time point after the trial starts between the intervention group and non-intervention group. Results: The background, rationale, and study design of this trial will be also presented. To date, over 100 patients have been enrolled in this trial. The entire study will end in 2020. Conclusion: The DUET trial will provide new evidence regarding the development of a treatment strategy using etelcalcetide for suitable control of iPTH levels and will define the optimal therapy for etelcalcetide-induced hypocalcemia in dialysis patients with SHPT.

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Aim: Recently, we demonstrated the efficacy of etelcalcetide in the control of secondary hyperparathyroidism (SHPT). This post hoc analysis aimed to evaluate changes in fibroblast growth factor-23 (FGF23) and calciprotein particles (CPPs) after treatment with calcimimetics. Methods: The DUET trial was a 12-week multicenter, open-label, parallel-group, randomized (1:1:1) study with patients treated with etelcalcetide plus active vitamin D (E + D group; n = 41), etelcalcetide plus oral calcium (E + Ca group; n = 41), or control (C group; n = 42) under maintenance haemodialysis. Serum levels of FGF23 and CPPs were measured at baseline, and 6 and 12 weeks after the start.Results: In the linear mixed model, serum levels of FGF23 in etelcalcetide users were significantly lower than those in non-users at week 6 (p < .001) and week 12 (p < .001). When compared the difference between the E + Ca group and the E + D group, serum levels of FGF23 in the E + Ca group were significantly lower than those in the E + D group at week 12 (p = .017). There were no significant differences in the serum levels of CPPs between etelcalcetide users and non-users at week 6 and week 12, while CPPs in the E + Ca group were significantly lower than those in the E + D group (p < .001) at week 12. Conclusion:Etelcalcetide may be useful through suppression of FGF23 levels among haemodialysis patients with SHPT. When correcting hypocalcaemia, loading oral calcium preparations could be more advantageous than active vitamin D for the suppression of both FGF23 and CPPs.