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Abstract: PO0375

Efficacy and Safety of Add-on Tenapanor to Phosphate Binders for Refractory Hyperphosphatemia in Japanese Patients on Hemodialysis: A Phase 2, Double-Blind Study

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Akizawa, Tadao, Showa University School of Medicine, Tokyo, Japan
  • Sato, Yu, Kyowa Kirin Co., Ltd., Tokyo, Japan
  • Takanuma, Masayuki, Kyowa Kirin Co., Ltd., Tokyo, Japan
  • Kanda, Hironori, Kyowa Kirin Co., Ltd., Tokyo, Japan
  • Fukagawa, Masafumi, Tokai University School of Medicine, Kanagawa, Japan
Background

Among hemodialysis (HD) patients, some patients have poorly controlled serum phosphorus levels, even while using phosphate binders (PB). Tenapanor is a novel agent, which reduces phosphate uptake by selectively inhibiting sodium/hydrogen exchanger isoform NHE3 on the apical surface of the enterocytes and then decreasing paracellular phosphate permeability. The mechanism of action is different from conventional PB used to treat hyperphosphatemia. The additional treatment of tenapanor is expected to reduce serum phosphorus levels in HD patients with poorly managed serum phosphorus levels by PB. Here, we evaluated the efficacy and safety of add-on tenapanor to PB for refractory hyperphosphatemia in patients on HD.

Methods

This was a multicenter, randomized, double-blind, placebo (PLA)-controlled, Ph2 study. The study consisted of a screening period, a 2 or 3-week observation period, and a 6-week treatment period. Patients whose serum phosphorus level was ≥6.1 and <10.0 mg/dL with PB were randomized to either tenapanor+PB or PLA+PB group in 1:1 ratio. Starting dose of tenapanor was 30 mg BID, which could be reduced in a step-wise manner (30, 20, 10 and 5 mg BID) at the investigator’s discretion, based on GI tolerability. The primary endpoint was the change in serum phosphorus level from baseline value at the end of treatment.

Results

47 subjects were randomized. Mean change in serum phosphorus level from baseline was −1.99 mg/dL in the tenapanor group and 0.08 mg/dL in the PLA group (95%CI −2.89, −1.26 mg/dL, p<0.001). The achievement ratio of target serum phosphorus level (≥3.5, ≤6.0 mg/dL) at the end of treatment was 87.0% in the tenapanor group and 37.5% in the PLA group. Diarrhea was the most frequent adverse event (tenapanor=65.2%; PLA=16.7%), all were of mild to moderate severity.

Conclusion

Tenapanor showed a significant decrease in serum phosphorus levels compared with PLA (p<0.001) under PB combination. This result suggests that coadministration of tenapanor with PB could satisfy the unmet needs to better control serum phosphorus in HD patients with refractory hyperphosphatemia.

Funding

  • Commercial Support