Abstract: TH-PO1045

Gastrointestinal Tolerability 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

Hyperphosphatemia (HP) is common in ESRD and associated with morbidity and mortality. Phosphate binders are commonly associated with gastrointestinal (GI) side effects including diarrhea, nausea, vomiting, dyspepsia, constipation, abdominal pain, and abdominal bloating. Tenapanor (TEN) is a minimally absorbed small molecule NHE3 inhibitor that reduces GI sodium and phosphate absorption.

Methods

8-week, double-blind, randomized treatment period (RT) with a 4-week placebo-controlled randomized withdrawal period (RW). Patients on hemodialysis (HD) with serum phosphate (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. Patient reporting of loosened stool or increased frequency in bowel movements (BMs), regardless of magnitude, was classified as “diarrhea.” Patients recorded daily BM frequency and form [Bristol Stool Form Score (BSFS)] using an eDiary.

Results

219 patients were randomized to RT, 164 entered RW, and 152 completed the study. There was only one TEAE observed in >5% of patients during RT (diarrhea, 39%) and no TEAE >5% during RW. During RT, 7.8% (n=17) of patients discontinued due to diarrhea; one (3 mg TEN) with SAE; during RW there were no discontinuations due to diarrhea. During RW, diarrhea was reported by 1.2% of the TEN group vs 2.4% on placebo and there were no discontinuations. Mean BM frequency increased by 0.4/day (baseline of 1.5/day) during RT, and BM frequency was 0.3/day higher with TEN than with placebo during RW. Mean BM frequency was within the normal range in all groups. Mean BSFS scores increased by 0.9 (baseline 4.2) during RT, and there was a 0.7-point difference between placebo (4.4) and TEN treatment (5.1) during RW.

Conclusion

TEN was well-tolerated in HD patients; the only TEAE >5% was diarrhea, reflecting the pharmacodynamic mechanism of action of TEN, resulting in softer more frequent BMs that, on average, remained within the normal range with regard to both frequency and form.

Funding

  • Commercial Support