Abstract: TH-PO146
Safety Analysis of Tenapanor Monotherapy vs. Sevelamer Carbonate in Patients on Maintenance Dialysis with Hyperphosphatemia
Session Information
- Bone and Mineral Metabolism: CKD-MBD Updates
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 502 Bone and Mineral Metabolism: Clinical
Authors
- Silva, Arnold L., Boise Kidney & Hypertension Institute, Nampa, Indiana, United States
- Hernandez, German T., El Paso Kidney Specialists, El Paso, Texas, United States
- Spiegel, David M., Ardelyx, Inc., Waltham, Massachusetts, United States
- Rosenbaum, David P., Ardelyx, Inc., Waltham, Massachusetts, United States
- Edelstein, Susan A., Ardelyx, Inc., Waltham, Massachusetts, United States
- Yang, Yang, Ardelyx, Inc., Waltham, Massachusetts, United States
- Zhao, Suling, Ardelyx, Inc., Waltham, Massachusetts, United States
- Williams, Laura, Ardelyx, Inc., Waltham, Massachusetts, United States
Background
Tenapanor (TEN) is a novel phosphate absorption inhibitor that blocks paracellular phosphate absorption by local inhibition of the intestinal sodium hydrogen exchanger isoform 3 (NHE3). TEN is being evaluated for the control of serum phosphate (sP) in adult patients (pts) with chronic kidney disease on maintenance dialysis. PHREEDOM (NCT03427125) was a phase 3 trial that evaluated TEN in pts on dialysis with HP. The phosphate binder (PB) sevelamer (SEV) was used as a safety control. Here we evaluate overall safety from PHREEDOM and present exposure-adjusted safety analyses.
Methods
The study design has been previously described. The trial enrolled pts on maintenance dialysis with sP ≤10.0 mg/dL and an sP increase ≥1.5 mg/dL after PB washout. The first 26 weeks was an open-label randomized treatment period (RTP) with pts randomized 3:1 to TEN 30 mg bid or SEV per package insert. Safety data collected during the RTP were from pts who received ≥1 dose of study drug. We calculated the exposure-adjusted incidence rates per 100 pt-years.
Results
Safety data is shown in the Table. 63.5% of pts randomized to the SEV arm (n=137) had received SEV prior to study entry. During the RTP, one death occurred in the TEN arm (n=419) due to a treatment-emergent adverse event (AE) unrelated to TEN. While the incidence of AEs leading to study drug discontinuation was higher in the TEN arm, the incidence of serious AEs (SAEs) and AEs leading to hospitalization was lower in the TEN arm than the SEV arm. The exposure-adjusted rates of SAEs were similar in both arms.
Conclusion
Incidence of AEs leading to hospitalization was lower in the TEN arm than the SEV arm. The analysis confirmed TEN has an acceptable safety profile.
| TEN (n=419) | SEV (n=137) | |
| Pt-years | 157.4 | 64.3 |
| Pts with any treatment-emergent AE (TEAE), n (%)* | 337 (80.4%) | 88 (64.2%) |
| Exposure-adjusted incidence rate of AEs per 100 pt-years | 214.1 | 136.9 |
| Pts with any serious TEAE, n (%) | 73 (17.4%) | 32 (23.4%) |
| Exposure-adjusted incidence rate of serious AEs per 100 pt-years | 46.4 | 49.8 |
| Pts with any TEAE leading to death, n (%) | 1 (0.2%) | 0 |
| Pts with any TEAE leading to study drug discontinuation, n (%) | 102 (24.3%) | 2 (1.5%) |
| Pts with any TEAE leading to hospitalization, n (%) | 73 (17.4%) | 32 (23.4%) |
| *63.5% of pts in the SEV arm had received SEV prior to study entry, potentially confounding the interpretation of AEs in favor of SEV, as demonstrated by the lower AE incidence than reported in its label. Serious AEs should have been largely unaffected by prior exposure. | ||
Funding
- Commercial Support – Ardelyx, Inc.