NaPi-IIb Inhibition for Hyperphosphatemia in CKD Hemodialysis Patients

Sonomi Maruyama; Thomas C Marbury; Jeffrey Connaire; Daniel Ries; William Maxwell; Curtis Rambaran

doi:10.1016/j.ekir.2020.12.017

NaPi-IIb Inhibition for Hyperphosphatemia in CKD Hemodialysis Patients

Kidney Int Rep. 2020 Dec 23;6(3):675-684. doi: 10.1016/j.ekir.2020.12.017. eCollection 2021 Mar.

Authors

Sonomi Maruyama¹, Thomas C Marbury², Jeffrey Connaire³, Daniel Ries⁴, William Maxwell¹, Curtis Rambaran¹

Affiliations

¹ Daiichi Sankyo, Inc., Basking Ridge, New Jersey, USA.
² Orlando Clinical Research Center, Orlando, Florida, USA.
³ DaVita Clinical Research, Minneapolis, Minnesota, USA.
⁴ Kidney Specialists of Minnesota, Minneapolis, Minnesota, USA.

Abstract

Introduction: Chronic kidney disease (CKD) has a prevalence of 9.1% globally, and frequently results in elevated serum phosphate, increasing cardiovascular morbidity and mortality risk in hemodialysis (HD) patients. DS-2330b, an oral NaPi-IIb inhibitor, reduced intestinal phosphate absorption in preclinical studies, but its effect in patients with CKD is unknown. This 2-part, randomized, placebo- and active-controlled, single- and repeated-dose, phase 1b study evaluated safety and efficacy of DS-2330b in patients with CKD on HD.

Methods: Part A, a 2-period, 2-way study, evaluated safety and pharmacokinetics of DS-2330b 250 mg in solution and tablet formulations. Part B assessed the safety of DS-2330b in solution (chosen based on results of part A) and its effect on serum phosphate. Patients were randomized to placebo 3 times daily (TID), DS-2330b 400 mg TID, DS-2330b 400 mg with sevelamer 1.6 g TID, and sevelamer 1.6 g with placebo TID for 14 days. Safety endpoints included adverse event (AE) monitoring.

Results: Six patients completed part A. Two patients experienced serious AEs considered unrelated to DS-2330b treatment. Thirty-two patients enrolled and completed part B. Serum phosphate mean change from baseline ± SD was -2.2±1.5 mg/dl versus -1.9 ± 1.1 mg/dl for DS-2330b monotherapy versus placebo. Patients receiving DS-2330b with sevelamer or sevelamer with placebo experienced the greatest serum phosphate decrease from baseline. Nine patients (28.1%) experienced ≥1 treatment-emergent AE (TEAE); 7 patients experienced drug-related TEAEs. The TEAE incidence was comparable between DS-2330b and control groups.

Conclusions: DS-2330b, alone or in combination with sevelamer, was safe and well tolerated but did not demonstrate clinically meaningful efficacy in HD patients.

Keywords: NaPi-IIb inhibitor; chronic kidney disease; clinical study; hemodialysis; hyperphosphatemia.