Tricida, Inc. announced the top-line results from its VALOR-CKD renal outcomes clinical trial, designed to evaluate veverimer's ability to slow CKD progression in patients with metabolic acidosis and chronic kidney disease (CKD). Primary Endpoint Analysis The VALOR-CKD trial did not meet its primary endpoint, which was defined as the time to the first occurrence of any event in the composite endpoint of renal death, end-stage renal disease (ESRD), or a confirmed greater than or equal to 40% reduction in estimated glomerular filtration rate (eGFR), also known as DD40. One hundred forty-nine veverimer- treated patients versus 148 placebo-treated patients experienced a DD40 primary endpoint event, representing a veverimer to placebo hazard ratio of 0.99 [95% CI, 0.78, 1.24; (p=0.898)] over the 26.7 months median duration of treatment.

The VALOR-CKD Trial Design The VALOR-CKD trial was an international, randomized, multicenter, double-blind, placebo-controlled trial of patients with CKD and metabolic acidosis. To qualify for enrollment in the study, patients were required to have two eGFR values, taken at least 2 weeks apart, in the range of 20 to 40 mL/min/1.73m(2), that were not more than 20% different from each other and three serum bicarbonate values, each taken at least 2 weeks apart from the others and all three within a 6- week period (the Screening Period), in the range of 12 to 20 mEq/L. The entry criteria for the study also required that patients be on a stable, maximum-tolerated, labeled dose of an angiotensin converting enzyme (ACE) inhibitor and/or angiotensin II receptor blocker (ARB) for at least 4 weeks prior to and during the Screening Period. Both patients taking oral alkali supplements and those not taking them were eligible for enrollment; however, a patient's use and dose of oral alkali was not to be changed during the study and those taking oral alkali were required to be on a stable dose for at least 2 weeks prior to and during the Screening Period.

There were no prohibited drugs. Eligible patients were enrolled into a single-blind active-treatment period of 4 to 8 weeks (Part A) that was followed by a randomized withdrawal into a double-blind, randomized treatment period (Part B). Patients in Part A who experienced a greater than or equal to 4 mEq/L increase from baseline in serum bicarbonate and those whose serum bicarbonate increased into the normal range of greater than or equal to 22 mEq/L at Week 4 were randomized in a 1:1 ratio either to continue treatment with veverimer or to treatment with placebo for the double-blind, Part B, portion of the trial.

Patients who did not achieve the required serum bicarbonate response to veverimer after 4 weeks in Part A continued to receive veverimer for an additional 4 weeks. After 8 weeks of veverimer treatment in Part A, those patients who experienced a greater than or equal to 4 mEq/L increase in serum bicarbonate and those whose serum bicarbonate increased into the normal range of greater than or equal to 22 mEq/L were randomized in a 1:1 ratio to either continued treatment with veverimer or to treatment with placebo in Part B. Those patients who did not achieve the desired serum bicarbonate response after 8 weeks in Part A discontinued treatment with veverimer and exited the study. In total, 2,198 patients received single-blind treatment with veverimer in Part A. Of these, 1,480 patients were randomized into Part B. The randomized patient population had a mean baseline eGFR of 29.2 mL/min/1.73m(2) and a mean baseline serum bicarbonate of 17.5 mEq/L. The majority of patients randomized in the trial had one or more co-morbid conditions, such as hypertension, heart failure or diabetes.

Approximately 12% of patients in the trial were taking oral alkali at baseline. The table below provides selected demographics and baseline characteristics of veverimer- and placebo-treated patients.