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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.

Ash SR, Singh B, Lavin PT, Stavros F, Rasmussen HS - Kidney Int. (2015)

Bottom Line: Current therapies are poorly tolerated and not always effective.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Indiana University Health Arnett, Lafayette, Indiana, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Serum parameters in 10-g ZS-9 (n=24) versus placebo (n=30) over 7 days. Mean change from baseline in (a) blood urea nitrogen, (b) serum bicarbonate, and (c) serum creatinine. Triangles indicate study drug administration (six doses in 48 h), and * indicates significant difference compared with placebo, P<0.05. ZS-9, sodium zirconium cyclosilicate.
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fig5: Serum parameters in 10-g ZS-9 (n=24) versus placebo (n=30) over 7 days. Mean change from baseline in (a) blood urea nitrogen, (b) serum bicarbonate, and (c) serum creatinine. Triangles indicate study drug administration (six doses in 48 h), and * indicates significant difference compared with placebo, P<0.05. ZS-9, sodium zirconium cyclosilicate.

Mentions: Baseline blood urea nitrogen was higher than placebo in the 10-g ZS-9 group (P=0.01) and similar in the other groups. There was evidence of a dose-related effect of ZS-9 on blood urea nitrogen; the greatest effect was in the 10-g group, with baseline decreases differing significantly from placebo at all measurements in days 2–7 (Figure 5a). Serum bicarbonate increased ∼10% with 10-g ZS-9, from 27.4 mmol/l at baseline to 30.1 mmol/l on days 2 (P=0.05) and 3 (P=0.067; Figure 5b).


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.

Ash SR, Singh B, Lavin PT, Stavros F, Rasmussen HS - Kidney Int. (2015)

Serum parameters in 10-g ZS-9 (n=24) versus placebo (n=30) over 7 days. Mean change from baseline in (a) blood urea nitrogen, (b) serum bicarbonate, and (c) serum creatinine. Triangles indicate study drug administration (six doses in 48 h), and * indicates significant difference compared with placebo, P<0.05. ZS-9, sodium zirconium cyclosilicate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526769&req=5

fig5: Serum parameters in 10-g ZS-9 (n=24) versus placebo (n=30) over 7 days. Mean change from baseline in (a) blood urea nitrogen, (b) serum bicarbonate, and (c) serum creatinine. Triangles indicate study drug administration (six doses in 48 h), and * indicates significant difference compared with placebo, P<0.05. ZS-9, sodium zirconium cyclosilicate.
Mentions: Baseline blood urea nitrogen was higher than placebo in the 10-g ZS-9 group (P=0.01) and similar in the other groups. There was evidence of a dose-related effect of ZS-9 on blood urea nitrogen; the greatest effect was in the 10-g group, with baseline decreases differing significantly from placebo at all measurements in days 2–7 (Figure 5a). Serum bicarbonate increased ∼10% with 10-g ZS-9, from 27.4 mmol/l at baseline to 30.1 mmol/l on days 2 (P=0.05) and 3 (P=0.067; Figure 5b).

Bottom Line: Current therapies are poorly tolerated and not always effective.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Indiana University Health Arnett, Lafayette, Indiana, USA.

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.

No MeSH data available.


Related in: MedlinePlus