|The following article is part of conference coverage from Kidney Week 2018 in San Diego hosted by the American Society of Nephrology. Renal & Urology News staff will be reporting live on medical studies conducted by nephrologists and other specialists who are tops in their field in acute kidney injury, chronic kidney disease, dialysis, transplantation, and more. Check back for the latest news from Kidney Week 2018.|
SAN DIEGO—An investigational drug that selectively binds hydrochloric acid in the gastrointestinal tract is safe and effective for treating metabolic acidosis in patients with chronic kidney disease (CKD), according to study findings presented at the American Society of Nephrology’s Kidney Week 2018 conference.
In a 12-week phase 3 randomized double-blind trial that included 217 CKD patients with metabolic acidosis, patients treated with an orally-dosed non-absorbed polymer with the investigational name TRC101 had a statistically significant greater increase in serum bicarbonate and self-reported physical functioning compared with patients who received placebo, a team led by Donald E. Wesson, MD, MBA, reported.
At baseline, the 217 patients had a mean serum bicarbonate level of 17.3 mEq/L and mean estimated glomerular filtration rate of 28.6 mL/min/1.73 m2. From baseline to week 12, mean serum bicarbonate increased by 4.5 mEq/L in the TRC101 arm compared with a rise of 1.7 mEq/L in the placebo group. Significantly more patients in the TRC101 than placebo group showed improvement in physical functioning as measured using the Kidney Disease Quality of Life Short Form-36 Physical Functioning subscale. Investigators observed a trend toward improvement in an objective measure of muscle function (the chair stand test), but this was not statistically significant.
A greater proportion of patients in the TRC101 than placebo arm experienced treatment-related adverse effects (13.7% vs 9.7%). Most of these effects were gastrointestinal, including diarrhea, flatulence, nausea, and constipation. The drug had no effect on other electrolytes or creatinine.
By removing hydrochloric acid from the GI tract, TRC101 stimulates the stomach to produce more bicarbonate that enters the systemic circulation. According to Dr Wesson, the drug will represent a significant advance in the treatment of metabolic acidosis in CKD patients.
“If we can get a 4 mEq/L increase in bicarbonate concentration in patients who have metabolic acidosis, that’s a hallelujah moment for us,” said Dr Wesson, Professor of Medicine at Texas A&M University College of Medicine and President of the Baylor Scott & White Health and Wellness Center in Dallas.
Traditionally, metabolic acidosis in patients with CKD is treated with oral sodium bicarbonate, which enters the systemic circulation and neutralizes the accumulated acid, and by reducing dietary acid intake.
“That way that we do it now requires a lot of bicarbonate pills, and many of our patients are not able to tolerate that many pills,” Dr Wesson told Renal & Urology News. “And even those who are able to tolerate the pill burden, many of them get gas and flatus because when that bicarbonate hits that hydrochloric acid, it produces gas in the stomach.”
Another challenge with sodium bicarbonate therapy is the sodium load that some CKD patients are unable to tolerate, he noted.
In contrast, TRC101 stays in the GI tract, where it binds hydrochloric acid and removes it from body via feces. Because it does not enter the systemic circulation, TRC101 causes much fewer adverse effects. “That’s one of the big reasons why the drug is so well tolerated,” Dr Wesson said.
The drug is being developed by Tricida, Inc., of South San Francisco, California, for which Dr Wesson is a paid consultant.
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Wesson DE, Mathur VS, Stasiv Y, et al. 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. Presented at the American Society of Nephrology’s Kidney Week 2018 conference in San Diego, Oct. 23-28. Abstract TH-PO1154.