麻豆传媒

ATLANTA -- A novel drug that selectively traps potassium ions may improve the treatment of hyperkalemia in patients with chronic kidney disease (CKD), researchers reported here.

In preliminary data from a phase III trial, three different doses of ZS-9 led to significantly greater declines in potassium levels over 48 hours, and the drug appeared safe over a 12-day period, , of Indiana University Health Arnett, and colleagues reported during a late-breaking session at .

Hyperkalemia is associated with significant mortality in patients with cardiovascular disease and chronic kidney disease, but current therapy -- the mainstay of which is sodium polystyrene sulfonate (Kayexalate) -- is poorly tolerated and not always effective, Ash said.

So Coppell, Texas-based developed an inorganic cation exchanger with a high selectivity for potassium, which the company says can bind nine times as much potassium as sodium polystyrene sulfonate -- an organic polymer resin. The drug comes as a fine powder that dissolves in water and is tasteless.

Ash presented results of a phase II study of the drug, as well as preliminary data from a larger phase III trial.

The phase II study looked at the safety and efficacy of three doses of the drug (0.3 grams, 3 grams, or 10 grams) compared with placebo in 90 patients with moderate CKD and mild-to-moderate hyperkalemia.

The primary endpoint was the difference in the rate of decline of serum potassium over 48 hours, and patients were followed through to day six for other safety and efficacy endpoints, including serum potassium at other time points, serum and urine electrolytes, BUN, and 24-hour urinary excretion.

There were no discontinuations and no serious adverse events. The lone moderate adverse event was mild constipation, which occurred in the 3-gram dosing group. There was, however, more vomiting with the 10g dose of the drug compared with all other groups.

Ash reported no cases of significant hypocalcemia, hypomagnesemia, or hypokalemia, and both the 3-gram and 10-gram doses met the primary endpoint of a significant decline in potassium compared with placebo (P=0.048 and P<0.0001, respectively).

The phase III trial enrolled 753 patients, some of whom had CKD and others who did not. They were randomized to placebo or to one of four doses of the drug (1.25 grams, 2.5 grams, 5 grams, and 10 grams) taken three times per day, and were followed for a total of 12 days.

The primary endpoint, again, was the drop in potassium levels over 48 hours, which was met with the three highest doses of the drug:

• 2.5 grams (-0.46 mEq/L, P=0.0009)
• 5 grams (-0.54 mEq/L, P<0.0001)
• 10 grams (-0.73 mEq/L, P<0.0001)

Ash said the drug was again well-tolerated and had a similar proportion of gastrointestinal adverse events to placebo when patients were followed for 12 days (3.5% and 5.1%).

He concluded that the drug "may provide a rapid and predictable treatment for hyperkalemia, with acceptable safety and tolerability."

, of in Farmington Hills, Mich., who was not involved in the study, told 麻豆传媒 the findings are likely to be "a big deal" since the drug may eventually top Kayexalate.

Topf said the phase III trial is the "largest potassium binder study ever," and also wondered whether it could be the "largest study on the treatment of hyperkalemia ever."

"Unless there are unforeseen safety signals, it looked pretty good," Topf told 麻豆传媒.

He also , that "given the , it will be great to have a safe, effective, and well-studied alternative."

Comment