Abstract: PO0376
Tolerability of Tenapanor, an Investigational, First-in-Class, Non-Binder Therapy for the Control of Serum Phosphorus in Patients with CKD on Dialysis
Session Information
- Biochemical Aspects of Mineral and Bone Disease
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Rosenbaum, David P., Ardelyx Inc, Fremont, California, United States
- Sprague, Stuart M., NorthShore University HealthSystem, Evanston, Illinois, United States
Background
Phosphate binders are associated with gastrointestinal (GI) tolerability issues including constipation, diarrhea, nausea, and vomiting. Tenapanor (TEN), a first in class, targeted therapy that blocks the paracellular absorption of phosphate in the GI tract by local inhibition of the sodium-hydrogen exchanger (NHE3), and may have a different GI profile because of its unique mechanism which also reduces dietary sodium absorption, increasing the sodium and water content of stool.
Methods
Data from a 12-week monotherapy study (TEN201), a 52-week monotherapy study (PHREEDOM), and a 4-week combination study (AMPLIFY) were analyzed to evaluate the GI tolerability of TEN. Adverse events were coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) (v 18, 20, 21). MedDRA classifies loose stool(s), loose bowel(s), and mushy stool(s) as diarrhea even without a reported increased frequency. Additionally, daily stool frequency and stool consistency using the Bristol Stool Form Scale (BSFS) were measured in TEN201.
Results
In each of the studies, the only adverse event that occurred in > 5% of TEN-treated patients was diarrhea as classified by MedDRA. Incidence of diarrhea during the treatment periods among patients on TEN 30 mg BID was 47.9%, 53.0%, and 42.7% for TEN201, PHREEDOM, and AMPLIFY, respectively, vs the placebo (PBO)-controlled randomized withdrawal period which was 2.9% vs. 2.4% in TEN201 and 4.0% vs. 1.6% in PHREEDOM, TEN vs. PBO, respectively. Across all studies, the diarrhea associated with TEN was most often mild-to-moderate and transient (with a median resolution within approximately 2 weeks); ~ 5% of patients experienced severe diarrhea. In TEN201, mean stool frequency increased by 2.8 bowel movements per week over baseline, and stool consistency increased by 0.8 points using the 7-point BSFS score, both remaining within the normal range.
Conclusion
These results demonstrate that TEN is associated with few GI side effects. Diarrhea, based on the MedDRA classification, occurred in approximately one-half of TEN-treated patients, most often reported as a modest and transient increase in stool frequency or loosening of stool.
Funding
- Commercial Support –