Patiromer, an orally administered potassium-binding polymer, significantly decreased serum potassium in adults who had diabetic kidney disease with hyperkalemia in a phase II study funded by and conducted with the manufacturer.
Patiromer consists of tiny, smooth beads in a liquid suspension and works by binding potassium throughout the GI tract, allowing it to be excreted in the feces. After preliminary studies demonstrated the agent’s usefulness in reducing hyperkalemia for up to 12 weeks in high-risk patients, researchers performed this open-label, uncontrolled trial to determine optimal dosing and to assess its longer-term safety. The findings were reported online July 14 in JAMA.
All four doses of patiromer studied significantly reduced serum potassium, beginning within 48 hours of the initial dose and continuing through all 52 weeks of treatment. The proportion of patients whose potassium levels reached target range at all scheduled visits ranged from 83% to 93% in those who had mild hyperkalemia at baseline and from 77% to 95% in those who had moderate hyperkalemia at baseline. Hyperkalemia quickly reappeared when patiromer treatment ended, reverting to baseline levels, wrote Dr. George L. Bakris of the ASH Comprehensive Hypertension Center, division of endocrinology, diabetes, and metabolism, University of Chicago, and his associates.
Study participants were 222 white patients with mild and 84 with moderate hyperkalemia (mean age, 66 years). All had type 2 diabetes and hypertension, and approximately one-third had heart failure; 65% had stage 3 and 22% had stage 4 chronic kidney disease (CKD), All were taking an ACE inhibitor, an angiotensin II receptor blocker, or both, with or without spironolactone. At 48 medical centers in five European countries, they were randomly assigned to receive one of four doses of patiromer that could be titrated up or down as needed for 4 weeks. Patients then entered an 8-week treatment phase, after which they continued maintenance therapy for a further 40 weeks (JAMA 2015 July 14 [ doi:10.1001/jama.2015.7446 ]).
The optimal doses of patiromer were found to be the two lowest doses assessed in this study, 8.4 g daily and 16.8 g daily, which significantly decreased serum potassium without provoking hypokalemia. These doses will now be tested in a phase III study.
The most frequent treatment-related adverse events in the phase II study were nonsevere hypomagnesemia (7.2%), constipation (4.6%), and diarrhea (2.7%). A total of 28 patients (9.2%) developed at least one adverse event prompting them to discontinue patiromer, including worsening of CKD (which was considered unrelated to treatment), hypokalemia (5 patients), and one hypertensive crisis (also unrelated to treatment). No dose-related edema was noted, and there were no clinically relevant changes in serum calcium or phosphate levels.