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Positive Pivotal Trial Data Reported for Patiromer FOS in Treatment of Hyperkalemia
Positive results from the pivotal phase III clinical trial program for Patiromer for Oral Suspension (Patiromer FOS, Relypsa, Inc.) –– a high-capacity oral potassium binder –– have been published in the New England Journal of Medicine.
The program was conducted under a special protocol assessment from the FDA to evaluate the safety and efficacy of Patiromer FOS for the treatment of hyperkalemia (HK) in patients with chronic kidney disease (CKD) receiving rennin–angiotensin–aldosterone system (RAAS) inhibitor therapy.
In October, a new drug application for Patiromer FOS was submitted to the FDA for the treatment of HK. If approved, it would be the first new therapy for HK in more than 50 years.
The two-part phase III clinical trial program was conducted under a special protocol assessment from the FDA. The treatment phase, in which all participants received Patiromer FOS, was a single-blind, single-arm trial in 243 patients with hyperkalemia and CKD who were also being treated with RAAS inhibitor medications. The study’s primary endpoint was the change in serum potassium from baseline to week 4. The secondary endpoint was the proportion of patients with a serum potassium level in the target range of 3.8 to less than 5.1 mEq/L at week 4.
The placebo-controlled, randomized maintenance phase of the program was designed to provide additional evidence for the efficacy of Patiromer FOS in treating hyperkalemia and to assess the need for chronic dosing. Patients from the treatment phase whose baseline serum potassium level was 5.5 mEq/L or more at enrollment and whose serum potassium level was controlled at week 4 were eligible for enrolment in the maintenance phase. These patients were randomly assigned to continue being treated with Patiromer FOS for an additional 8 weeks or to receive placebo for 8 weeks. The primary endpoint was the between-group difference in the change in serum potassium from baseline to week 4 or to an earlier time point when the subject first had a serum potassium level of less than 3.8 mEq/L or at least 5.5 mEq/L.
All trial endpoints were met in the two-part program.
In the treatment phase, the mean change in the serum potassium level was −1.01 mEq/L (P < 0.001) in 237 evaluable patients receiving Patiromer FOS. At week 4, 76% of the patients were within the target potassium level (3.8 to less than 5.1 mEq/L). Subsequently, 107 patients were randomly assigned to Patiromer FOS (n = 55) or placebo (n = 52) for the maintenance phase. Of note during this phase, the Patiromer FOS group had no change in median potassium from baseline, but in the placebo group, median serum potassium increased (P < 0.001). Further, a recurrence of hyperkalemia (serum potassium level of 5.5 mEq/L or greater) was observed in 60% of the patients in the placebo group compared with 15% of those in the Patiromer FOS group through week 8 (P < 0.001).
In a pre-specified analysis, 44% patients in the placebo group compared with 94% in the Patiromer FOS group were still receiving RAAS inhibitor therapy at the end of the study.
Mild-to-moderate constipation was the most common adverse event, occurring in 11% of the patients in the treatment phase and in 4% of those in the Patiromer FOS group in the maintenance phase. Importantly, there was no evidence of drug-induced edema or urinary-tract infections. The hypokalemia rate over the 4-week treatment period was low (3%), and no patients in the maintenance phase experienced hypokalemia. No serious drug-related adverse events were reported in either the treatment or the maintenance phase.
In addition to the two-part phase III program, Patiromer FOS has been evaluated in CKD patients with hyperkalemia in a 12-month phase II study and in a 48-hour phase I onset-of-action trial. In all of these studies, Patiromer FOS met its efficacy endpoints and the treatment was well tolerated.
Source: Relypsa, Inc.; November 21, 2014.