Kidney Week

Abstract: TH-PO1154

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Treat Metabolic Acidosis in CKD Patients with TRC101, a Novel, Non-Absorbed, Hydrochloric Acid Binder

Session Information

• Late-Breaking Clinical Trials Posters
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• No subcategory defined

Authors

• Wesson, Donald E., Baylor Scott and White Health and Wellness Center, Dallas, Texas, United States

Donald E. Wesson,

• Mathur, Vandana S., Mathur Consulting, Woodside, California, United States

Vandana S. Mathur,

• Stasiv, Yuri, Tricida, Inc., South San Francisco, California, United States

Yuri Stasiv,

• Parsell, Dawn, Parsell and Otto Consulting, Inc., Cedar Park, Texas, United States

Dawn Parsell,

• Klaerner, Gerrit, Tricida, Inc., South San Francisco, California, United States

Gerrit Klaerner,

• Bushinsky, David A., University of Rochester Medical Center, Rochester, New York, United States

David A. Bushinsky,

Background

Metabolic acidosis increases risk of chronic kidney disease (CKD) progression and adversely affects muscle and bone. TRC101, a non-absorbed, sodium-free polymeric drug that selectively binds and removes hydrochloric acid from the gastrointestinal tract, is being developed for the treatment of metabolic acidosis in CKD and slowing CKD progression.

Methods

217 CKD patients (eGFR 20 - 40 mL/min/1.73m²) with metabolic acidosis (serum bicarbonate [HCO₃] 12 - 20 mEq/L) were randomized 4:3 to TRC101 (6 g) or placebo once-daily for 12 weeks. Algorithmic dose titration was performed to achieve a normal serum HCO₃ (22 - 29 mEq/L). The primary endpoint was the between-group comparison of the proportion of patients with a ≥4 mEq/L increase in serum HCO₃ or a normal serum HCO₃ at Week 12. The secondary endpoint evaluated the change from baseline in serum HCO₃. Two exploratory endpoints evaluated effects of acidosis correction on physical functioning using the Kidney Disease Quality of Life Short Form-36 Physical Functioning subscale and a timed repeated chair stand test.

Results

The mean (SD) baseline serum HCO3 and eGFR were 17.3 (1.5) mEq/L and 28.6 (6.0) mL/min/1.73m2, respectively. 96% of patients completed treatment. Comorbidities included hypertension (97%), diabetes (65%), left ventricular hypertrophy (44%), and congestive heart failure (31%). More TRC101 (59.2%) than placebo (22.5%) patients met the primary endpoint response definition (p<0.0001). From baseline to Week 12, mean serum HCO3 increased +4.5 mEq/L (TRC101) vs. +1.7 mEq/L (placebo), p<0.0001. More TRC101 compared with placebo patients had improvement in self-reported physical functioning (p = 0.012) and there was a trend toward improvement in standardized chair stand time (p=0.063). There were no effects of TRC101 on creatinine or other electrolytes. Overall treatment-related adverse events occurred in 9.7% of placebo and 13.7% of TRC101 patients, most of which were gastrointestinal (e.g., diarrhea, flatulence, nausea and constipation).

Conclusion

TRC101 effectively and safely treated metabolic acidosis and improved self-reported physical functioning in CKD patients.

Funding

• Commercial Support – Tricida, Inc. San Francisco, CA, USA