Dataset Information

NaPi-IIb Inhibition for Hyperphosphatemia in CKD Hemodialysis Patients.

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.

SUBMITTER: Maruyama S

PROVIDER: S-EPMC7938184 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

NaPi-IIb Inhibition for Hyperphosphatemia in CKD Hemodialysis Patients.

Maruyama Sonomi S Marbury Thomas C TC Connaire Jeffrey J Ries Daniel D Maxwell William W Rambaran Curtis C

Kidney international reports 20201223 3

<h4>Introduction</h4>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 efficac ...[more]

PMID: 33732982

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Dataset Information

NaPi-IIb Inhibition for Hyperphosphatemia in CKD Hemodialysis Patients.

Introduction

Methods

Results

Conclusions

Publications

NaPi-IIb Inhibition for Hyperphosphatemia in CKD Hemodialysis Patients.

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