A Randomized Trial of Tenapanor and Phosphate Binders as a Dual-Mechanism Treatment for Hyperphosphatemia in Patients on Maintenance Dialysis (AMPLIFY)

J Am Soc Nephrol. 2021 Jun 1;32(6):1465-1473. doi: 10.1681/ASN.2020101398. Epub 2021 Mar 25.


Background: Hyperphosphatemia is associated with cardiovascular morbidity and mortality in patients receiving maintenance dialysis. It is unknown whether combining two therapies with different mechanisms of action-tenapanor, an inhibitor of paracellular phosphate absorption, and phosphate binders-is safe and effective for the management of hyperphosphatemia in patients receiving maintenance dialysis.

Methods: This double-blind phase 3 trial enrolled 236 patients undergoing maintenance dialysis with hyperphosphatemia (defined in this trial as serum phosphorus 5.5-10 mg/dl inclusive) despite receiving phosphate binder therapy (sevelamer, nonsevelamer, sevelamer plus nonsevelamer, or multiple nonsevelamer binders). These participants were randomly assigned to receive oral tenapanor 30 mg twice daily or placebo for 4 weeks. The primary efficacy end point was the change in serum phosphorus concentration from baseline to week 4.

Results: Of the 236 randomized patients, 235 (99.6%) were included in the full analysis set; this included 116 in the tenapanor plus binder group and 119 in the placebo plus binder group. A total of 228 patients (96.6%) completed the 4-week treatment period. In the full analysis set (mean age 54.5 years, 40.9% women), patients treated with tenapanor plus binder achieved a larger mean change in serum phosphorus concentration from baseline to week 4 compared with placebo plus binder (-0.84 versus -0.19 mg/dl, P<0.001). Diarrhea was the most commonly reported adverse event, resulting in study drug discontinuation in four of 119 (3.4%) and two of 116 (1.7%) patients receiving tenapanor plus binder or placebo plus binder, respectively.

Conclusions: A dual-mechanism treatment using both tenapanor and phosphate binders improved control of hyperphosphatemia in patients undergoing maintenance dialysis compared with phosphate binders alone.

Clinical trial registry name and registration number: AMPLIFY, NCT03824587.

Keywords: FGF23; NHE3 dialysis; hyperphosphatemia; phosphate binders; phosphate uptake; phosphorus; tenapanor.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chelating Agents / adverse effects
  • Chelating Agents / therapeutic use*
  • Diarrhea / chemically induced
  • Double-Blind Method
  • Drug Therapy, Combination / adverse effects
  • Female
  • Fibroblast Growth Factor-23
  • Humans
  • Hyperphosphatemia / blood
  • Hyperphosphatemia / drug therapy*
  • Isoquinolines / adverse effects
  • Isoquinolines / therapeutic use*
  • Male
  • Middle Aged
  • Phosphorus / blood
  • Renal Dialysis*
  • Renal Insufficiency, Chronic / therapy
  • Sevelamer / therapeutic use
  • Sodium-Hydrogen Exchanger 3 / antagonists & inhibitors
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*


  • Chelating Agents
  • FGF23 protein, human
  • Isoquinolines
  • Sodium-Hydrogen Exchanger 3
  • Sulfonamides
  • Phosphorus
  • Fibroblast Growth Factor-23
  • Sevelamer
  • tenapanor

Associated data

  • ClinicalTrials.gov/NCT03824587