Efficacy and safety of PT20, an iron-based phosphate binder, for the treatment of hyperphosphataemia: a randomized, double-blind, placebo-controlled, dose-ranging, Phase IIb study in patients with haemodialysis-dependent chronic kidney disease

Abstract

Abstract Background Hyperphosphataemia is a common complication of chronic kidney disease (CKD). PT20 (ferric iron oxide adipate) is an investigational molecule engineered to offer enhanced phosphate-binding properties relative to other phosphate binders. Methods In this double-blind, parallel-group, placebo-controlled, dose-ranging study (ClinicalTrials.gov identifier NCT02151643), the efficacy and safety of 28 days of oral PT20 treatment were evaluated in patients with dialysis-dependent CKD. Participants were randomly assigned in an 8:8:8:13:13 ratio to receive PT20 (400, 800, 1600 or 3200 mg) or placebo three times daily. Results Among 153 participants, 129 completed treatment [7 discontinued because of adverse events (AEs), 2 because of hyperphosphataemia and 15 for other reasons]. PT20 treatment for 28 days resulted in a statistically significant and dose-dependent reduction in serum phosphate concentration. There were no statistically significant effects of PT20 treatment on changes in haemoglobin or ferritin concentrations or transferrin saturation between Days 1 and 29. The incidence of treatment-emergent AEs was broadly similar across the PT20 and placebo groups (42–59% versus 44%). The most common PT20 treatment-related AEs were gastrointestinal, primarily diarrhoea (13–18%) and discoloured faeces (3–23%). No serious AEs were considered to be related to study treatment. There were no clinically significant changes in laboratory results reflecting acid/base status or increases in ferritin that could indicate the absorption of components of PT20. Conclusions In this first study investigating the efficacy and safety of PT20 in patients with hyperphosphataemia and dialysis-dependent CKD, PT20 significantly lowered serum phosphate concentrations and was generally well tolerated.