Abstract: TH-PO1046

Efficacy of Tenapanor to Treat Hyperphosphatemia in Patients on Hemodialysis

Session Information

Category: Mineral Disease

  • 1201 Mineral Disease: Ca/Mg/PO4

Authors

  • Block, Geoffrey A., Denver Nephrology, Denver, Colorado, United States
  • Rosenbaum, David P., Ardelyx, Inc., Fremont, California, United States
  • Korner, Paul, Ardelyx, Inc., Fremont, California, United States
  • Yan, Zhiwu, Ardelyx, Inc., Fremont, California, United States
  • Chertow, Glenn Matthew, Stanford University School of Medicine, Palo Alto, California, United States
Background

Tenapanor (TEN) is a minimally absorbed oral small molecule that blocks the sodium-hydrogen type 3 exchanger (NHE3) in the gastrointestinal (GI) tract inhibiting the absorption of dietary sodium and has been demonstrated to alter paracellular phosphate transport and reduce serum phosphate (sP) concentration in patients receiving hemodialysis (HD).

Methods

8-week, double-blind, randomized treatment period (RT) with a 4-week placebo-controlled randomized withdrawal period (RW). Patients on HD with sP ≥6.0 mg/dL and a 1.5 mg/dL increase from baseline were randomized 1:1:1 to receive 3, 10 or 30 mg TEN twice daily. The 30 mg cohort was allowed to down-titrate weekly (30 to 20 to 15 to 10 to 3 mg twice daily) during the first 4 weeks of RT based on GI tolerability. At the end of RT all patients were re-randomized 1:1 to either remain on TEN or placebo for RW. The primary endpoint, based on the responder population (defined as patients demonstrating a ≥1.2 mg/dL decrease in sP during RT), was the difference in change in sP between pooled TEN and placebo from the end of RT to the end of RW.

Results

219 patients receiving HD were randomized and 164 patients (75%) completed RT, of which 152 (93%) completed RW. Principal reasons for discontinuation included adverse events (8%), and hyperphosphatemia (5%). 80 patients were responders in whom the mean decrease in sP as compared to baseline during RT was 2.6 mg/dL. During RW, mean sP increased by 1.5 mg/dL in placebo treated patients and 0.5 mg/dL in TEN treated patients, resulting in a LS mean difference of –0.8 (95% CI: –1.4, –0.2, p=0.01). For the intent to treat (ITT) group (all 164 patients in RW), mean sP increased by 0.8 mg/dL in placebo treated patients and 0.1 mg/dL in those receiving TEN resulting in a LS mean difference of –0.7 (95% CI: –1.2, –0.3, p=0.003). TEN resulted in statistically significant reductions in sP during RT in all 3 TEN groups.

Conclusion

TEN, an oral small molecule NHE3 inhibitor that reduces intestinal phosphate transport, significantly lowers sP in patients receiving HD with hyperphosphatemia.

Funding

  • Commercial Support