Among patients with diabetic kidney disease and hyperkalemia (elevated potassium levels in the blood), a potentially life-threatening condition, those who received the new drug patiromer, twice daily for four weeks, had significant decreases in potassium levels which lasted through one year, according to a study in the July 14 issue of JAMA.
Patients at the highest risk for hyperkalemia are those taking renin-angiotensin-aldosterone system (RAAS) inhibitors with stage 3 or greater chronic kidney disease (CKD) who also have diabetes mellitus, heart failure, or both. Because of the limited utility of current options to manage hyperkalemia, particularly over the long term, clinicians frequently must either avoid using RAAS inhibitors or use them at lower than recommended doses, according to background information in the article. Use of RAAS can help further slow progression of renal disease among patients with diabetes.
Patiromer is an orally administered drug being investigated for the treatment of hyperkalemia. The active portion, patiromer, is a non-absorbed polymer that binds potassium throughout the gastrointestinal tract, thus increasing excretion of potassium in the stool and lowering serum potassium levels. Prior patiromer clinical trials have demonstrated the drug's utility in treating hyperkalemia in other at-risk populations for periods ranging from a few days to up to 12 weeks.
George L. Bakris, M.D., of University of Chicago Medicine, Chicago, and colleagues randomly assigned 306 outpatients with type 2 diabetes and an elevated serum potassium level to 1 of 3 starting doses of patiromer twice daily. All patients received RAAS inhibitors prior to and during study treatment. The phase 2 trial was conducted at 48 sites in Europe from June 2011 to June 2013.
The researchers found that patiromer significantly reduced serum potassium levels across dose groups (8.4 - 33.6 g/d) through week 4 in patients with a varying severity of hyperkalemia, and consistently maintained normal serum potassium levels over 52 weeks. Over this period, patiromer use demonstrated high adherence, low risk of hypokalemia (abnormally low level of potassium in the blood), and minimal discontinuations because of adverse events.
Over the 52 weeks, hypomagnesemia (abnormally low level of magnesium in the blood; 7 percent) was the most common treatment-related adverse event, mild to moderate constipation (6 percent) was the most common gastrointestinal adverse event, and hypokalemia occurred in 6 percent of patients.
The authors note that based on the findings of this study, a phase 3 study was performed in which patiromer demonstrated consistent efficacy as shown in this study. "The consistency of results across the secondary end points [including average change in serum potassium level through 52 weeks] supports the conclusions regarding long-term efficacy."
In an accompanying editorial, Wolfgang C. Winkelmayer, M.D., Sc.D., of the Baylor College of Medicine, Houston, and Associate Editor, JAMA, comments on the findings of this study.
"Once hyperkalemia drugs are approved based on trials of the surrogate of potassium concentration, it is uncertain if the manufacturers will be motivated to conduct such crucial trials of the hard end points that patients care about (reduced progression of CKD and deferral of dialysis; better heart failure outcomes), especially if the alternative is to spend the same dollars on marketing and company-sponsored and -directed contract research of their already-approved product. Thus, as part of the approval process, the FDA and other agencies should consider mandating a sizeable postmarketing trial and safety surveillance program to clearly establish whether the assumptions underlying the value proposition of chronic hyperkalemia treatments actually hold."
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