San Diego—The risk of chronic kidney disease (CKD) progression is increased in patients with metabolic acidosis, and metabolic acidosis 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 to treat metabolic acidosis and slow the progression of CKD.
Donald E. Wesson, MD, MBA, of the Baylor Scott and White Health and Wellness Center, Dallas, Texas, reported results of a phase 3, double-blind, placebo-controlled trial of TRC101 in patients with CKD and metabolic acidosis in a late-breaking poster session at Kidney Week 2018. The poster was titled 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.
A total of 217 patients with CKD with metabolic acidosis were randomized in a 4:3 ratio to receive 6g TRC101 or placebo once-daily for 2 weeks. Algorithmic dose titration was performed to achieve a normal serum bicarbonate (HCO3) level of 22 to 29 mEq/L.
The primary end point of interest 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 change from baseline in serum HCO3 was a secondary end point. There were two exploratory end points evaluating the effects of acidosis correction on physical functioning (measured by the Kidney Disease Quality of Life Short Form-36 Physical Functioning subscale) and a timed repeated chair stand test.
Mean baseline serum HCO3 was 17.3 mEq/L and mean baseline estimated glomerular filtration rate was 28.6 mL/min/1.73 m2. Of the 217 patients, 96% completed the study. Comorbidities were hypertension (97%), diabetes (65%), left ventricular hypertrophy (44%), and congestive heart failure (31%).
The primary end point response definition was met by 59.2% of patients in the TRC101 group compared with 22.5% of those in the placebo group (P<.0001). Mean serum HCO3 increased 4.5 mEq/L the TRC101 group versus 1.7 mEq/L in the placebo group from baseline to week 12 (P<.0001).
Compared with patients in the placebo group, more patients in the TRC101 group reported improvement in physical functioning (P=.012) and there was a trend toward improvement in standardized chair stand time in the TRC101 group (P=.063). There was no effect on creatinine or other electrolytes. Adverse events occurred in 9.7% of patients in the placebo group and 13.7% of patients in the TRC101 group; most of the adverse events were gastrointestinal.
“TRC101 effectively and safely treated metabolic acidosis and improved self-reported physical functioning in CKD patients,” the researchers said.
Source: Wesson DE, Mathur VS, Stasiv Y, Parsell D, Klaerner G, Bushinsky DA. 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. Abstract of a late-breaking poster (TH-PO1154) presented at the American Society of Nephrology Kidney Week 2018, October 25, 2018, San Diego, California.
This study was funded by Tricida, Inc.