Randomized Study of Tenapanor Added to Phosphate Binders for Patients With Refractory Hyperphosphatemia

INTRODUCTION: Serum phosphorus management is important for patients with chronic kidney disease on dialysis to reduce the risk of hyperparathyroidism and ectopic vascular calcification. Phosphate binders (PBs) control serum phosphorus levels; however, some patients do not achieve adequate control with existing PBs. The similar mechanisms of action of each PB may limit their ability to lower serum phosphorus levels. Therefore, drugs with novel mechanisms of action that can be added to existing PBs to further lower serum phosphorus levels are desired. Tenapanor, a novel selective inhibitor of intestinal sodium/hydrogen exchanger 3 transporters, decreases passive phosphate absorption in the intestine, thereby decreasing serum phosphorus levels. METHODS: This study evaluated the efficacy and safety of tenapanor treatment with up-titration when added to PBs among Japanese hemodialysis patients with hyperphosphatemia poorly controlled by PBs alone. In total, 169 patients taking PBs whose serum phosphorus level was ≥6.1 and <10.0 mg/dl initiated the 8-week treatment (placebo + PB, n = 85; tenapanor + PB, n = 84). RESULTS: The least squares mean change from baseline to week 8 in serum phosphorus level was −0.24 and −2.00 mg/dl in the placebo and tenapanor groups, respectively, with a statistically significant difference between groups (−1.76 mg/dl; P < 0.0001). Diarrhea as a treatment-emergent adverse event (TEAE) occurred in 14.1% and 63.1% of patients in the placebo and tenapanor groups, respectively. All diarrhea events were mild or moderate. CONCLUSION: Tenapanor added to PBs improved serum phosphorus levels that could not previously be controlled by PBs alone, and no new safety concerns were raised.