Patiromer FOS, made by Relypsa Inc., significantly reduced blood potassium from baseline levels in patients with moderate-to-severe hyperkalemia (mean blood potassium levels at baseline: 5.93 mEq/L), who had chronic kidney disease and were taking at least one renin angiotensin aldosterone system (RAAS) inhibitor, according to a study published Sept. 16 in Kidney International.
Patiromer FOS started to decrease potassium levels at four hours (the first evaluation time point) and the reduction became statistically significant at seven hours. The reduction in blood potassium levels was significant at all following time points during the 48-hour treatment period (p≤0.004 for hours 7 and 10; p<0.001 for hours 12-48) and was sustained for 24 hours after the last dose. Patiromer FOS was well tolerated with a safety profile consistent with that observed in other clinical trials.
If approved, Patiromer will be the first new treatment for hyperkalemia in more than 50 years.
A year-long study, published in JAMA July 14, of more than 300 patients with hyperkalemia, hypertension, type 2 diabetes, and chronic kidney disease found that the investigational can reduce elevated blood-potassium levels.
“Consistent with previously published studies, we also observed that when patients stopped taking Patiromer FOS their blood potassium levels increased, providing further evidence of the medication’s potassium-lowering effect and highlighting the need for chronic treatment,” said David A. Bushinsky, MD, lead author of the paper, and a Professor of Medicine and of Pharmacology and Physiology at the University of Rochester School of Medicine, and Chief of the Nephrology Division at the University of Rochester Medical Center.
The study was among eight clinical trials included in the New Drug Application submitted to the U.S. Food and Drug Administration for Patiromer FOS. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of Oct. 21, 2015.
Patiromer is made of small smooth spherical beads, about one-tenth of a millimeter in diameter—the size of a typical dust particle. When mixed with a few tablespoons of water and swallowed, these particles attach themselves to potassium ions in the lower part of the colon, where the concentration of free potassium is the highest. The potassium-packed beads are then excreted.
Hyperkalemia study design and results
The Phase 1 open-label, single-arm study evaluated the time to onset of the potassium-lowering action of Patiromer FOS in 25 CKD patients with moderate-to-severe hyperkalemia who were taking at least one RAAS inhibitor. It was conducted in inpatient clinical research units. Prior to starting treatment, patients were in the unit for 3 days on a strictly controlled low potassium and low sodium diet. Those with sustained hyperkalemia, despite the diet (baseline blood potassium levels >5.5 and <6.5 mEq/L), received 8.4 g of Patiromer FOS with morning and evening meals, a total of four doses over 48 hours, followed by a 7-day post-treatment follow-up period. The change from baseline in blood potassium levels was assessed at multiple time points during the 48-hour treatment period, including an initial assessment at 4 hours after the first dose and then every 2 to 4 hours.
- The mean baseline blood potassium level was 5.93 mEq/L.
- The study met its primary endpoint and showed a rapid and significant reduction in patients’ blood potassium levels at 7 hours after the first dose of Patiromer FOS (p=0.004) and at every following time point during the 48-hour treatment period (p ≤0.004 for hours 7 and 10; p <0.001 for hours 12-48) and for 24 hours after the last dose.
- A decrease in potassium levels that was first observed at four hours, the first evaluation time point.
- At 48 hours (14 hours after the last dose), mean blood potassium had fallen by 0.75 mEq/L (p<0.001), and more than 90%of patients had values ≤5.5 mEq/L.
- Over the entire treatment period, mean blood potassium levels continued to decrease, with no increase before the next dose or for 24 hours after the last dose.
- A significant increase in mean blood potassium was observed 4 and 7 days after the last dose of Patiromer FOS.
- Patiromer FOS was well tolerated. All 25 patients completed the study and no serious or severe adverse events were reported. The most common adverse events were mild constipation (in two patients) and mild hypotension (in two patients). No hypokalemia (serum potassium <3.5 mEq/L) or hypomagnesemia (<1.4 mg/dL) were observed.