Novel oral hyperkalemia drug shows promise in phase III trial

The oral drug sodium zirconium cyclosilicate may offer an effective new treatment option for outpatients with mild hyperkalemia, according to results of the phase III, open-label, randomized HARMONIZE trial presented at the American Heart Association scientific sessions.

The sodium-potassium cation exchanger zirconium cyclosilicate reduced potassium levels in 258 patients with mild hyperkalemia to normal levels within 48 hours, compared with placebo, and effectively maintained potassium levels for up to 4 weeks. The findings were published simultaneously in JAMA (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15688]). However, more long-term studies are needed to assess the efficacy and safety of the drug beyond 4 weeks and in patients with more severe hyperkalemia, reported Dr. Mikhail Kosiborod of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., and his colleagues.

In the open-label phase of the study, 258 outpatients with hyperkalemia (serum potassium ≥5.1 mEq/L) were given 10 g of zirconium cyclosilicate three times a day for 48 hours. Mean serum potassium levels significantly declined by 0.2 mEq/L 1 hour after the initial dose and decreased an average 1.1 mEq/L at 48 hours, with 98% (n = 237) of patients achieving normokalemia (3.5-5.0 mEq/L). These patients were then randomized to receive 5 g (n = 45), 10 g (n = 51), or 15 g (n = 56) of zirconium cyclosilicate or placebo (n = 85) daily, and were followed for 28 days.

Zirconium cyclosilicate lowered serum potassium to 4.8, 4.5, and 4.4 mEq/L at 5, 10, and 15 g, respectively, compared with 5.1 mEq/L for placebo. Adverse events were comparable between the treatment and placebo groups, but edema was more common in the 15-g group. Hyperkalemia developed in 10% of the 10-g group and 11% of the 15-g group, compared with no patients in the 5-g or placebo groups.

In an accompanying editorial, Dr. Bradley S. Dixon of the University of Iowa, Iowa City, said the findings suggest that zirconium cyclosilicate may offer an important new treatment for the acute and short-term treatment of outpatients with mild hyperkalemia. “Longer-term studies are needed to assess the clinical benefits and risks that may be related to more extended use of this product, especially among hospitalized patients, as well as those with more severe hyperkalemia, other medical conditions, and other medications that affect potassium homeostasis,” he wrote.

The study was sponsored and funded by ZS Pharma, maker of sodium zirconium cyclosilicate. Dr. Kosiborod reported serving as a consultant for ZS Pharma and as an investigator on the HARMONIZE study. Several coauthors also declared financial interests with ZS Pharma. Dr. Dixon reported financial relationships with multiple companies, but not with ZS Pharma.

The oral drug sodium zirconium cyclosilicate may offer an effective new treatment option for outpatients with mild hyperkalemia, according to results of the phase III, open-label, randomized HARMONIZE trial presented at the American Heart Association scientific sessions.

The sodium-potassium cation exchanger zirconium cyclosilicate reduced potassium levels in 258 patients with mild hyperkalemia to normal levels within 48 hours, compared with placebo, and effectively maintained potassium levels for up to 4 weeks. The findings were published simultaneously in JAMA (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15688]). However, more long-term studies are needed to assess the efficacy and safety of the drug beyond 4 weeks and in patients with more severe hyperkalemia, reported Dr. Mikhail Kosiborod of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., and his colleagues.

In the open-label phase of the study, 258 outpatients with hyperkalemia (serum potassium ≥5.1 mEq/L) were given 10 g of zirconium cyclosilicate three times a day for 48 hours. Mean serum potassium levels significantly declined by 0.2 mEq/L 1 hour after the initial dose and decreased an average 1.1 mEq/L at 48 hours, with 98% (n = 237) of patients achieving normokalemia (3.5-5.0 mEq/L). These patients were then randomized to receive 5 g (n = 45), 10 g (n = 51), or 15 g (n = 56) of zirconium cyclosilicate or placebo (n = 85) daily, and were followed for 28 days.

Zirconium cyclosilicate lowered serum potassium to 4.8, 4.5, and 4.4 mEq/L at 5, 10, and 15 g, respectively, compared with 5.1 mEq/L for placebo. Adverse events were comparable between the treatment and placebo groups, but edema was more common in the 15-g group. Hyperkalemia developed in 10% of the 10-g group and 11% of the 15-g group, compared with no patients in the 5-g or placebo groups.

In an accompanying editorial, Dr. Bradley S. Dixon of the University of Iowa, Iowa City, said the findings suggest that zirconium cyclosilicate may offer an important new treatment for the acute and short-term treatment of outpatients with mild hyperkalemia. “Longer-term studies are needed to assess the clinical benefits and risks that may be related to more extended use of this product, especially among hospitalized patients, as well as those with more severe hyperkalemia, other medical conditions, and other medications that affect potassium homeostasis,” he wrote.

The study was sponsored and funded by ZS Pharma, maker of sodium zirconium cyclosilicate. Dr. Kosiborod reported serving as a consultant for ZS Pharma and as an investigator on the HARMONIZE study. Several coauthors also declared financial interests with ZS Pharma. Dr. Dixon reported financial relationships with multiple companies, but not with ZS Pharma.

The oral drug sodium zirconium cyclosilicate may offer an effective new treatment option for outpatients with mild hyperkalemia, according to results of the phase III, open-label, randomized HARMONIZE trial presented at the American Heart Association scientific sessions.

The sodium-potassium cation exchanger zirconium cyclosilicate reduced potassium levels in 258 patients with mild hyperkalemia to normal levels within 48 hours, compared with placebo, and effectively maintained potassium levels for up to 4 weeks. The findings were published simultaneously in JAMA (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15688]). However, more long-term studies are needed to assess the efficacy and safety of the drug beyond 4 weeks and in patients with more severe hyperkalemia, reported Dr. Mikhail Kosiborod of Saint Luke’s Mid America Heart Institute in Kansas City, Mo., and his colleagues.

In the open-label phase of the study, 258 outpatients with hyperkalemia (serum potassium ≥5.1 mEq/L) were given 10 g of zirconium cyclosilicate three times a day for 48 hours. Mean serum potassium levels significantly declined by 0.2 mEq/L 1 hour after the initial dose and decreased an average 1.1 mEq/L at 48 hours, with 98% (n = 237) of patients achieving normokalemia (3.5-5.0 mEq/L). These patients were then randomized to receive 5 g (n = 45), 10 g (n = 51), or 15 g (n = 56) of zirconium cyclosilicate or placebo (n = 85) daily, and were followed for 28 days.

Zirconium cyclosilicate lowered serum potassium to 4.8, 4.5, and 4.4 mEq/L at 5, 10, and 15 g, respectively, compared with 5.1 mEq/L for placebo. Adverse events were comparable between the treatment and placebo groups, but edema was more common in the 15-g group. Hyperkalemia developed in 10% of the 10-g group and 11% of the 15-g group, compared with no patients in the 5-g or placebo groups.

In an accompanying editorial, Dr. Bradley S. Dixon of the University of Iowa, Iowa City, said the findings suggest that zirconium cyclosilicate may offer an important new treatment for the acute and short-term treatment of outpatients with mild hyperkalemia. “Longer-term studies are needed to assess the clinical benefits and risks that may be related to more extended use of this product, especially among hospitalized patients, as well as those with more severe hyperkalemia, other medical conditions, and other medications that affect potassium homeostasis,” he wrote.

The study was sponsored and funded by ZS Pharma, maker of sodium zirconium cyclosilicate. Dr. Kosiborod reported serving as a consultant for ZS Pharma and as an investigator on the HARMONIZE study. Several coauthors also declared financial interests with ZS Pharma. Dr. Dixon reported financial relationships with multiple companies, but not with ZS Pharma.