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Abstract: PO0382

Dose-Response Efficacy and Tolerability of Tenapanor on Hyperphosphatemia in Japanese Hemodialysis Patients: Results of a Randomized Phase 2 Study

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Inaguma, Daijo, Fujita Health University School of Medicine, Aichi, 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
  • Akizawa, Tadao, Showa University School of Medicine, Tokyo, Japan
Background

Tenapanor is a novel, non-binder, targeted therapy that reduces paracellular phosphate absorption in the gut by selectively inhibiting the intestinal sodium/hydrogen exchanger isoform NHE3. In a US clinical trial by Ardelyx, Inc. tenapanor significantly reduced serum phosphorus level in hemodialysis (HD) patients with hyperphosphatemia as compared to the placebo (PLA). The purpose of this study was to confirm the efficacy, dose-response and tolerability of tenapanor on hyperphosphatemia in Japanese HD patients.

Methods

This was a multicenter, randomized, double-blind, PLA-controlled, parallel-group and dose-finding Ph2 study. The study consisted of a screening, a 2 or 3-week 1st washout (WO) period, a 6-week treatment period, and a 3-week 2nd WO period. Patients were enrolled when screening serum phosphorus level was 3.5−6.0 mg/dL and increased by ≥1.0 mg/dL to 6.1−9.9 mg/dL after 1st WO. Thereafter patients were randomized to one of 5 groups (PLA, tenapanor 5 mg, 10 mg, 30 mg or 30 mg down titration (DT) twice/day). 30 mg DT group could be down-titrated in a step-wise manner to 20, 10 and 5 mg on the basis of GI tolerability. The primary endpoint was the mean change in serum phosphorus level from baseline to end of treatment in each group.

Results

207 subjects were enrolled (41 or 42 subjects were randomized to each group). The mean change in serum phosphorus at the end of treatment from baseline was 0.64 mg/dL in the PLA group, −0.93 mg/dL in the 5 mg group, −1.36 mg/dL in the 10 mg group, −1.92 mg/dL in the 30 mg group and −1.99 mg/dL in the 30 mg DT group (p<0.001 in all tenapanor groups vs PLA). The major adverse event was diarrhea, which occurred in a dose-dependent manner (PLA: 22.0%, tenapanor 5 mg: 57.1%, 10 mg: 65.9%, 30 mg: 76.2%, 30 mg DT: 70.7%). Most of the events were mild in severity, and, in each tenapanor group, only 1 to 3 subjects were discontinued from the study due to diarrhea.

Conclusion

Tenapanor was well tolerated in Japanese HD patients and significantly decreased serum phosphorus level in a dose-dependent manner compared with PLA (p<0.001).

Funding

  • Commercial Support