#346 Oxylanthanum carbonate for hyperphosphatemia in ESKD: tolerability trial in progress

Abstract

Abstract Background and Aims Despite current therapies, more than 43% of patients undergoing dialysis in the USA have hyperphosphatemia, defined as serum phosphate values >5.5 mg/dL and is commonly associated with an increased risk of death. Most currently available phosphate binders are known to cause gastrointestinal (GI) adverse events (AEs) that can negatively impact the patient experience. Common GI AEs include abdominal pain, nausea, and bloating. Phosphate binders are usually formulated as large tablets, and some must be chewed before ingestion. Commonly a high number of pills are needed per day to achieve goal serum phosphate levels. Oxylanthanum carbonate (OLC) is a new lanthanum-based nanotechnology product in development with a high in vitro binding capacity as compared to other phosphate binders. OLC is formulated as a small pill that is swallowed whole instead of being chewed before swallowing as is the case for lanthanum carbonate. The safety of OLC has been studied in >100 healthy subjects. The most common treatment-related AE (>5%) in an OLC bioequivalence (BE) study was nausea. This study aims to evaluate the tolerability of clinically effective (serum phosphate ≤5.5 mg/dL) doses of OLC in patients on hemodialysis. Method This open-label, single-arm, multicenter, multidose study will enroll up to 90 patients on hemodialysis who require phosphate binder therapy and have mean historical serum phosphate levels between ≥4.0 and ≤7.0 mg/dL for ≥8 weeks. The primary endpoint of the study is tolerability as assessed by the incidence of discontinuations due to treatment-related AEs. Additionally, the incidence of AEs related to OLC will be collected. Participants will undergo up to 3 weeks of phosphate binder washout until their serum phosphate levels reach >5.5 and ≤10.0 mg/dL (Fig. 1). During the 6-week Titration Period, all patients will receive 1500 mg/day OLC (500 mg TID with meals/snacks) for the initial 2 weeks, with subsequent titration every 2 weeks until achieving a target serum phosphate level (≤5.5 mg/dL) or to a maximum OLC dose of 3000 mg/day. After titration, patients will enter a 4-week Maintenance Period at the effective OLC dose. Results We intend to present results elucidating tolerability of clinically effective doses of OLC in patients on dialysis. Conclusion The tolerability of OLC at doses effective in achieving a serum phosphate ≤5.5 mg/dL in patients on hemodialysis will be evaluated in this study.