Study identifier:ZS-003
ClinicalTrials.gov identifier:NCT01737697
EudraCT identifier:N/A
CTIS identifier:N/A
Multicenter, Two-phase, Multi-dose, Prospective, Randomized, Double-blind, Placebo-Controlled Study of Safety and Efficacy of Microporous, Fractionated, Protonated Zirconium Silicate in Mild to Moderate Hyperkalemia
Hyperkalemia
Phase 3
No
Zirconium silicate (acute phase), Zirconium silicate (subacute phase), Placebo (acute phase), Placebo ( subacute phase)
All
754
Interventional
18 Years +
Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Supportive Care
Verified 01 May 2018 by ZS Pharma, Inc.
ZS Pharma, Inc.
-
Acute Phase: It is hypothesized that ZS (zirconium silicate) is more effective than placebo control (alternative hypothesis) in lowering S-K levels in subjects with S-K between 5.0 - 6.5 mmol/l versus no difference between ZS and placebo control (null hypothesis). Subacute Phase (randomized withdrawal): It is hypothesized that ZS once daily is more effective than placebo control (alternative hypotheses) in maintaining normokalemic levels (3.5 - 4.9 mmol/l) among subjects completing the Acute Phase versus no difference between each ZS dose and respective placebo controls (null hypotheses).
A total of 750 subjects with mild to moderate hyperkalemia (i- STAT potassium levels between 5.0-6.5 mmol/l, inclusive) will be enrolled in the study where they, in a double-blind fashion, will be randomized 1:1:1:1:1 to receive one of four (4) doses of ZS (1.25g, 2.5g, 5g, and 10g) or placebo control, administered 3 times daily (tid) with meals for the initial 48 hours (Acute Phase), followed by a Subacute Phase (randomized withdrawal) during which patients treated with active doses in the Acute Phase, who achieve normokalemia (i-STAT potassium values 3.5 to 4.9 mmol/l, inclusive) will be randomized to 12 days of subacute, once a day (qd) dosing. There will be a one-time randomization to assign the Acute Phase treatment and the Subacute Phase treatment. The Subacute Phase will include subjects who became normokalemic on active drug and those who became normokalemic on placebo. The former will be randomized in a 1:1 ratio between the same dose of ZS they received during the acute phase but only administered once a day (qd) or placebo, qd. Subjects on placebo during the Acute Phase who are normokalemic in the morning of Study Day 3, will be randomized to receive either 1.25 or 2.5 g ZS, qd as Subacute Phase treatment. Safety and tolerability will be assessed on an ongoing basis by an Independent Data Safety Monitoring Board (DSMB). Each active dose group will consist of 150 patients per treatment group including the placebo control group for a total of 750 patients; the 1:1:1:1:1 allocation helps to optimize the multiple active dose comparisons to the respective placebo controls for the Subacute Phase.
Location
Location
Edgewater, Florida, United States, 32123
Location
Orangeburg, South Carolina, United States, 29118
Location
Summerfield, Florida, United States, 34491
Location
Lakeland, Florida, United States, 33805
Location
Miami, Florida, United States, 33169
Location
Sumter, South Carolina, United States, 29150
Location
St. Petersburg, Florida, United States, 33709
Location
Anniston, Alabama, United States, 36207
Arms | Assigned Interventions |
---|---|
Experimental: Zirconium silicate (acute phase) Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered 3 times (tid) daily with meals for 48 hours. | Drug: Zirconium silicate (acute phase) Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered 3 times (tid) daily with meals for 48 hours. Other Name: ZS |
Placebo Comparator: Placebo (acute phase) Placebo ( silicified microcrystalline cellulose) randomized to mimic doses of experimental drug administered 3 times (tid) daily with meals. | Drug: Placebo (acute phase) Randomized to mimic doses of experimental drug administered 3 times (tid) daily with meals for 48 hours during the acute phase. Other Name: Silicified microcrystalline cellulose |
Experimental: Zirconium silicate (subacute phase) Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered once a day prior to the morning meal for 12 days. | Drug: Zirconium silicate (subacute phase) Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered once a day prior to the morning meal for 12 days. Other Name: ZS |
Placebo Comparator: Placebo (subacute phase) Placebo (silicified microcrystalline cellulose) randomized to mimic doses of experimental drug administered once a day (qd) prior to the morning meal for 12 days. | Drug: Placebo ( subacute phase) Randomized to mimic doses of experimental drug administered once a day prior to the morning meal for 12 days during the subacute phase. Other Name: Silicified microcrystalline cellulose |
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