title: A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient.
abstract: Hyperkalemia contributes to significant mortality and limits the use of cardioprotective and renoprotective renin-angiotensin-aldosterone blockers. Current therapies are poorly tolerated and not always effective. Here we conducted a phase 2 randomized, double-blind, placebo-controlled dose-escalation study to assess safety and efficacy of ZS-9. This oral selective cation exchanger that preferentially entraps potassium in the gastrointestinal tract was given to patients with stable Stage 3 chronic kidney disease and hyperkalemia (5.0 to 6.0 mEq/l) during a 2-day period. Of 90 eligible patients with mean baseline serum potassium of 5.1 mEq/l, 30 were randomized to placebo, 12-0.3 g, 24-3 g, or 24 to 10 g of ZS-9 three times daily for 2 days with regular meals. None withdrew and ZS-9 dose-dependently reduced serum potassium. The primary efficacy end point (rate of serum potassium decline in the first 48 h) was met with significance in the 3- and 10-g cohorts. From baseline, mean serum potassium was significantly decreased by 0.92±0.52 mEq/l at 38 h. Urinary potassium excretion significantly decreased with 10-g ZS-9 as compared to placebo at day 2 (+15.8 +/- 21.8 vs. +8.9 +/- 22.9 mEq per 24h) from placebo at day 2. In this short-term study, no serious adverse events were reported; only mild constipation in the 3-g dose group was possibly related to treatment. Thus, ZS-9 was well-tolerated in patients with stable chronic kidney disease and hyperkalemia leading to a rapid, sustained reduction in serum potassium.
authors: Department of Nephrology, Indiana University Health Arnett, Lafayette, Indiana, USA.
authors: Stephen R
authors: SR
authors: Ash
authors: 1] Apex Research of Riverside, Riverside, California, USA [2] ZS Pharma, Coppell, Texas, USA.
authors: Bhupinder
authors: B
authors: Singh
authors: Boston Biostatistics Research Foundation, Framingham, Massachusetts, USA.
authors: Philip T
authors: PT
authors: Lavin
authors: ZS Pharma, Coppell, Texas, USA.
authors: Fiona
authors: F
authors: Stavros
authors: ZS Pharma, Coppell, Texas, USA.
authors: Henrik S
authors: HS
authors: Rasmussen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017920:Antiporters / Q000008:administration & dosage* / Q000009:adverse effects; D003248:Constipation / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood* / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D017640:Silicates / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D017920:Antiporters; D017640:Silicates; C000597310:sodium zirconium cyclosilicate; D011188:Potassium
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