Dose-Response of Tenapanor in Patients With Hyperphosphatemia Undergoing Hemodialysis in Japan—A Phase 2 Randomized Trial

Introduction: Simplified, but effective, hyperphosphatemia treatments with novel mechanisms of action, tolerable safety profiles, and low pill burden are needed for patients undergoing hemodialysis. Tenapanor is a calcium (Ca)-free, nonmetal, nonpolymeric drug that reduces phosphate absorption by selectively inhibiting intestinal sodium-hydrogen exchanger 3. As the serum phosphorus (P) level-lowering effect of tenapanor has not been evaluated in Japanese patients with hyperphosphatemia undergoing hemodialysis, we evaluated its efficacy and safety in this population. Methods: This was a multicenter, phase 2, double-blind, placebo-controlled, parallel-group, dose-finding study. Change in serum P level from baseline at week 6 was the primary end point. Results: Overall, 207 patients were randomized to 5 groups (placebo [n = 41] and tenapanor 5-mg taken twice daily [BID] [n = 42], 10-mg BID [n = 41], 30-mg BID [n = 42], and 30-mg BID dose-titration [n = 41]) and treated for 6 weeks. Mean changes from baseline at week 6 in serum P level were 0.64, -0.93, -1.36, -1.92, and -1.99 mg/dl in the placebo and tenapanor groups, respectively. Serum P level was significantly decreased from baseline in all tenapanor groups compared with placebo (P < 0.001, for each dose). Diarrhea was the most frequent drug-related adverse event (AE) with an incidence of 9.8%, 50.0%, 65.9%, 76.2%, and 65.9% in the respective placebo and tenapanor groups. Conclusion: In Japanese patients undergoing hemodialysis, tenapanor was found to have a dose-responsive, serum P level-lowering effect. Diarrhea was the most frequent drug-related AE; most cases were mild and generally tolerable. Tenapanor may become a first-in-class therapeutic agent for patients with hyperphosphatemia.