Abstract: SA-PO400
Tenapanor Plus Phosphate Binder Reduces Interdialytic Weight Gain (IDWG) in Patients With CKD on Hemodialysis (HD): Post Hoc Analysis of the AMPLIFY Study
Session Information
- Hemodialysis and Frequent Dialysis: CV and Risk Prediction
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 701 Dialysis: Hemodialysis and Frequent Dialysis
Authors
- Fishbane, Steven, Zucker School of Medicine, Great Neck, New York, United States
- Fadem, Stephen Z., Kidney Associates, PLLC/Baylor College of Medicine, Houston, Texas, United States
- Yang, Yang, Ardelyx, Inc., Waltham, Massachusetts, United States
- Edelstein, Susan A., Ardelyx, Inc., Waltham, Massachusetts, United States
- Spiegel, David M., Ardelyx, Inc., Waltham, Massachusetts, United States
Background
Excessive IDWG in patients with CKD on HD is associated with poor outcomes. Tenapanor, a novel investigational phosphate absorption inhibitor (PAI), inhibits intestinal NHE3 and increases stool Na and water content. To assess whether tenapanor might decrease IDWG and allow patients to achieve target dry weight, we performed post hoc analysis of pre-HD weights from the phase 3 AMPLIFY study (NCT03824587). We hypothesized that, compared to phosphate binder treatment alone, CKD patients treated with tenapanor and phosphate binder would have decreased IDWG and more easily approach target dry weight as reflected by a pre-HD weight decrease.
Methods
In AMPLIFY, patients with CKD on dialysis with high serum phosphorus (despite phosphate binder treatment) were randomized to add tenapanor 30 mg bid or placebo to their treatment regimen for 4 weeks. Pre-HD weights were recorded at baseline and week 4 after a short interdialytic interval. We evaluated the impact of tenapanor on pre-HD weight over the 4-week study.
Results
At week 4, mean pre-HD weight decreased with tenapanor and increased with placebo (Table), and weight percent change differed significantly between tenapanor and placebo groups (LS mean difference: −0.81%, P=0.0284; Table). At week 4, pre-HD weight decreased by a greater percentage in the tenapanor vs placebo groups (Table), and pre-HD weights decreased in a greater number of patients from the tenapanor group and increased in a greater number from the placebo group (Figure).
Conclusion
These results suggest that tenapanor may reduce IDWG. The potential to control serum phosphorus while helping patients achieve target weight may be beneficial for patients on HD.
| Treatment group | Baseline mean (SD) pre-HD weight, kg | Week 4 mean (SD) pre-HD weight, kg | LS mean (SE) pre-HD weight percent change, % | LS mean difference (SE) in percent change, ANCOVA P value* | Patients with any decrease in pre-HD weight at week 4, n (%) | Odds ratio, CMH test P value** |
| Tenapanor + phosphate binder (n=103) | 96.2 (23.0) | 95.8 (23.0) | −0.24 (0.27) | −0.81 (0.37) P=0.0284 | 58 (56.3) | 2.06 P=0.0126 |
| Placebo + phosphate binder (n=107) | 90.0 (26.6) | 90.2 (26.3) | 0.57 (0.29) | 45 (42.1) | ||
| *P value, LS means, and SEs were obtained from an ANCOVA model with sex, phosphate binder type, and treatment as factors and baseline pre-HD weight as a covariate. **P value was obtained from CMH test controlling for sex and phosphate binder type. ANCOVA, analysis of covariance; CMH, Cochran-Mantel-Haenszel; HD, hemodialysis; LS, least squares; SD, standard deviation; SE, standard error. | ||||||
Funding
- Commercial Support – Ardelyx, Inc.