title: Bixalomer in Hyperphosphatemic Patients With Chronic Kidney Disease Not on Dialysis: Phase 3 Randomized Trial.
abstract: Currently, calcium- or metal-containing phosphate binders are available to treat hyperphosphatemia in predialysis patients with chronic kidney disease. Bixalomer, a non-calcium, metal-free phosphate binder, has not been studied in these patients. We evaluated the efficacy and safety of bixalomer versus placebo for treatment of hyperphosphatemia in Japanese predialysis patients with chronic kidney disease. This multicenter, randomized, double-blind, phase 3 trial, randomized eligible patients 1:1 to receive bixalomer or placebo for 12 weeks. Bixalomer was started at 1500 mg/day and adjusted up to 7500 mg/day depending on serum phosphorus concentrations. The primary endpoint was change in serum phosphorus concentration from baseline to end of treatment. After a 4-week pre-investigational period, 163 patients (bixalomer: N = 81; placebo: N = 82) were randomized. The adjusted mean change (95% confidence interval) from baseline to end of treatment in serum phosphorus was significantly greater with bixalomer (-0.78 [-0.98, -0.57] mg/dL) versus placebo (0.20 [-0.00, 0.41] mg/dL); mean difference: -0.98 (-1.27, -0.69), P < 0.001. At end of treatment, 57.5% of bixalomer-treated patients achieved target serum phosphorus concentrations, mean serum intact parathyroid hormone and fibroblast growth factor-23 decreased, and there were no significant changes in corrected serum calcium. The safety and tolerability of bixalomer was similar to placebo. The most common drug-related adverse events were gastrointestinal (>24% patients per group). There was a significant increase in bicarbonate concentrations with bixalomer versus placebo (P = 0.003). Bixalomer was superior to placebo for hyperphosphatemia in Japanese predialysis patients with chronic kidney disease and may constitute a new treatment option.
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
authors.affiliation: Division of Biostatistics and Clinical Epidemiology, University of Toyama School of Medicine|, Toyama, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Origasa
authors.affiliation: Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Kameoka
authors.affiliation: Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Junko
authors.identifier: http://orcid.org/0000-0003-1635-9408
authors.initials: J
authors.lastname: Tsukada
authors.affiliation: Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Kentarou
authors.initials: K
authors.lastname: Kuroishi
authors.affiliation: Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yamaguchi
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054559:Hyperphosphatemia / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000627:therapeutic use*; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D016896:Treatment Outcome
chemical_list: D011073:Polyamines; C000589735:bixalomer
keywords: Bixalomer; Chronic kidney disease; Hyperphosphatemia; Phosphate binder; Predialysis