Kidney Week

Abstract: SA-OR070

TRC101, a Novel Hydrochloric Acid Binder, Increases Serum Bicarbonate in Acidemic Patients with CKD

Session Information

• Tipping the Balance: Fluid and Electrolytes in Health and Disease
  November 04, 2017 | Location: Room 385, Morial Convention Center
  Abstract Time: 06:18 PM - 06:30 PM

Category: Fluid, Electrolytes, and Acid-Base

• 704 Fluid, Electrolyte, Acid-Base Disorders

Authors

• Bushinsky, David A., Univ. of Rochester, Rochester, New York, United States

David A. Bushinsky, MD

• Hostetter, Thomas H., Case Western Reserve Univ., Cleveland, Ohio, United States

Thomas H. Hostetter,

• Alpern, Robert Jay, Yale School of Medicine, New Haven, Connecticut, United States

Robert Jay Alpern,

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

Gerrit Klaerner,

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

Yuri Stasiv,

• Lockey, Claire, Tricida, Inc., South San Francisco, California, United States

Claire Lockey,

• McNulty, Sarah, Tricida, Inc., South San Francisco, California, United States

Sarah McNulty,

• Lee, Angela A, Tricida, Inc., South San Francisco, California, United States

Angela A Lee,

• Parsell, Dawn, Parsell Associates, Cedar Park, Texas, United States

Dawn Parsell,

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

Vandana S. Mathur,

• Buysse, Jerry M., Tricida, Inc., South San Francisco, California, United States

Jerry M. Buysse,

Background

Metabolic acidosis is common in patients with chronic kidney disease (CKD) and has significant adverse effects on renal function, muscle, and bone. TRC101 is a novel, orally-administered, non-absorbed, metal and counterion-free polymer that selectively binds hydrochloric acid. In this study of acidemic CKD patients we evaluated the safety and tolerability of TRC101, and its effectiveness in increasing serum bicarbonate.

Methods

In this randomized, double-blind, placebo-controlled study, 135 acidemic CKD patients (eGFR 20 to <60 mL/min/1.73m²) were admitted to an in-patient unit and treated for 14 days with placebo (BID or QD) or one of four TRC101 dosing regimens (1.5, 3.0, or 4.5 g BID; 6.0 g QD), while on a controlled diet. After completion of treatment, patients were discharged and followed for up to 14 days.

Results

Patients had a mean baseline eGFR of 34.8 mL/min/1.73m² and a mean baseline serum bicarbonate of 17.7 mEq/L. Comorbidities included hypertension (93%), diabetes (70%), and heart failure (22%). Within 72 hours of the first TRC101 dose, mean serum bicarbonate increased in each of the four TRC101 treatment groups by >1.4 mEq/L and was significantly increased (p<0.0001) by 3.1 - 3.8 mEq/L at the end of treatment compared to placebo. Mean serum bicarbonate continued to increase in all treatment groups over the course of the study while the mean bicarbonate in the placebo group remained stable. In the combined TRC101 treatment groups, serum bicarbonate was in the normal range (22 - 29 mEq/L) at the end of treatment in 34.6% of patients and increased by >4 mEq/L in 38.5% of patients. After discontinuation of TRC101, serum bicarbonate decreased nearly to baseline levels within 2 weeks. All adverse events were mild or moderate in intensity and there were no serious or severe adverse events. All patients completed the study.

Conclusion

In this 14-day study of acidemic CKD patients TRC101 was safe and well-tolerated and led to a significant increase in the level of serum bicarbonate.

Funding

• Commercial Support – Tricida