OBJECTIVES: In patients on maintenance dialysis, hyperphosphatemia is a risk factor for mortality and hospitalization. Tenapanor is an investigational, first-in-class, phosphate absorption inhibitor, providing a novel, non-binder approach to treating hyperphosphatemia. The PHREEDOM study was a long-term Phase 3 trial evaluating the safety and efficacy of tenapanor to treat hyperphosphatemia in patients on maintenance dialysis (hemo- or peritoneal dialysis). This post-hoc analysis aims to identify the effects of tenapanor relative to sevelamer on hospitalization and length of stay.

METHODS: The PHREEDOM study was a 52-week study consisting of a 26-week, open-label, randomized treatment period with a 12-week placebo-controlled randomized withdrawal period, followed by a 14-week open label safety extension period. Patients on maintenance dialysis with serum phosphorus ≥ 6.0 mg/dL and a 1.5 mg/dL increase in serum phosphorus following phosphate binder washout were randomized 3:1 to receive one 30 mg tenapanor tablet twice daily or sevelamer per package insert for a 52-week period. At end of randomized treatment period, all patients in the tenapanor arm were re-randomized 1:1 to tenapanor or placebo for the randomized withdrawal period, followed by tenapanor for the safety extension period. Sevelamer was used as a safety control for the comparison of serious adverse events and hospitalizations. Results followed the intention-to-treat principle.

RESULTS: The proportion of patients who experienced any serious adverse event leading to hospitalization at 26 weeks was 17.4% in patients receiving tenapanor and 23.4% in patients receiving sevelamer; the average duration of hospitalization was longer in patients receiving sevelamer, compared to patients receiving tenapanor (9.75 days ± 9.8 days vs. 8.86 days ± 8.28 days).

CONCLUSIONS: Patients randomized to tenapanor had lower rates of hospitalization and shorter lengths of stay when hospitalization occurred, relative to patients randomized to sevelamer.