search
Back to results

Safety & Efficacy of Zirconium Silicate in Mild to Moderate Hyperkalemia

Primary Purpose

Hyperkalemia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Zirconium silicate (acute phase)
Zirconium silicate (subacute phase)
Placebo (acute phase)
Placebo ( subacute phase)
Sponsored by
ZS Pharma, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Hyperkalemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provision of written informed consent.
  • Over 18 years of age.
  • Mean i-STAT potassium values between 5.0 - 6.5 mmol/l inclusive, at screening (Study Day 0).
  • Ability to have repeated blood draws or effective venous catheterization.
  • Women of childbearing potential must be practicing a highly effective method of birth control.

Exclusion Criteria:

  • Pseudohyperkalemia signs and symptoms, such as excessive fist clinching hemolyzed blood specimen, severe leukocytosis or thrombocytosis.
  • Subjects treated with lactulose, xifaxan or other nonabsorbed antibiotics for hyperammonemia within the last 7 days.
  • Subjects treated with resins (such as Sevelamer acetate or Sodium polystyrene sulfonate [SPS; e.g. Kayexalate®]), calcium acetate, calcium carbonate, or lanthanum carbonate, within the last 7 days.
  • Subjects with a life expectancy of less than 3 months.
  • Subjects who are HIV positive.
  • Subjects who are severely physically or mentally incapacitated and who in the opinion of investigator are unable to perform the subjects' tasks associated with the protocol.
  • Women who are pregnant, lactating, or planning to become pregnant.
  • Subjects with Ketoacidosis/Acidemia.
  • Presence of any condition which, in the opinion of the investigator, places the subject at undue risk or potentially jeopardizes the quality of the data to be generated.
  • Known hypersensitivity or previous anaphylaxis to ZS or to components thereof.
  • Previous treatment with ZS
  • Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry.
  • Subjects with cardiac arrhythmias that require immediate treatment.
  • Insulin-dependent diabetes mellitus
  • Subjects on dialysis

Sites / Locations

  • Pinnacle Research Group
  • Saadat Ansari Internal Medicine
  • Aspire Clinical Studies, LLC
  • Southwest Clinical Research Institute
  • California Institute of Renal Research
  • Torrance Clinical Research
  • Academic Medical Research Institute
  • Mohammad Ismail, Inc
  • Apex Research of Riverside
  • Capital Nephrology Clinical Group
  • Pikes Peak Nephrology Associates
  • Denver Nephrologists, PC
  • Nephrology and Hypertension Associates
  • JEM Research Institute
  • Clinical Research of Brandon
  • Meridien Research
  • Riverside Clinical Research
  • Endocrinology of Central Florida
  • Meridien Research
  • San Marcus Research Clinic
  • Medical Consulting Center
  • Elite Research Institute
  • Prevention & Strengthening Solutions, Inc
  • PCCC of Volusia
  • Meridien Research
  • Lakeview Medical Research
  • Clinical Research Trials of Florida
  • Metabolic Research Institute
  • Research by Design
  • Professional Research Network of Kansas, LLC
  • Washington Nephrology Associates
  • Nephrology Center DBA, Paragon Health PC
  • The Center for Clinical Trials
  • Clinical Research Consultants, LLC
  • United Medical Associates
  • Life Medi-Research and Management
  • Doylestown Hospital Medical Research
  • South Carolina Nephrology & Hypertension
  • Carolina Diabetes and Kidney Center
  • Southwest Houston Research, Ltd
  • Clinical Advancement Center, PLLC
  • Southern Utah Kidney and Hypertension Center
  • Renal Research
  • Melbourne Renal Research Group

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Zirconium silicate (acute phase)

Placebo (acute phase)

Zirconium silicate (subacute phase)

Placebo (subacute phase)

Arm Description

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.

Placebo ( silicified microcrystalline cellulose) randomized to mimic doses of experimental drug administered 3 times (tid) daily with meals.

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.

Placebo (silicified microcrystalline cellulose) randomized to mimic doses of experimental drug administered once a day (qd) prior to the morning meal for 12 days.

Outcomes

Primary Outcome Measures

Exponential Rate of Change in Serum Potassium (S-K) Levels During the Initial 48 Hours of Study Drug Treatment.
Exponential Rate of Change in S-K Levels in the Subacute Phase.

Secondary Outcome Measures

Percentage of Subjects Who Achieve Normalization in S-K Levels After 48 Hours of Treatment
Mean Change From Baseline in S-K at All Time Points Acute Phase
Mean change from baseline in S-K at all time points over initial 48 hours
Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase
Mean percent change from baseline in S-K at all time points over initial 48 hours
Time Subjects Remain Normokalemic (Subacute Phase)
Time (number of days) subjects remain normokalemic (3.5 - 5.0 mmol/l) subacute phase
Percentage of Subjects Within Each Treatment Group Who Retained Normal S-K Values at End of Subacute Phase
Percentage of subjects within each treatment group who retained normal S-K values (values between 3.5-5.0 mmol/L) at end of subacute phase
Mean Change From Subacute Baseline in Serum Potassium at All Time Points.
Mean change from subacute baseline in serum potassium at all time points during subacute phase
Mean Percent Change From Subacute Baseline in Serum Potassium at All Time Points.
Mean percent change from subacute baseline in serum potassium at all time points during subacute phase

Full Information

First Posted
November 19, 2012
Last Updated
September 14, 2018
Sponsor
ZS Pharma, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT01737697
Brief Title
Safety & Efficacy of Zirconium Silicate in Mild to Moderate Hyperkalemia
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
November 30, 2012 (Actual)
Primary Completion Date
October 31, 2013 (Actual)
Study Completion Date
November 30, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ZS Pharma, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperkalemia

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
754 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zirconium silicate (acute phase)
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo (acute phase)
Arm Type
Placebo Comparator
Arm Description
Placebo ( silicified microcrystalline cellulose) randomized to mimic doses of experimental drug administered 3 times (tid) daily with meals.
Arm Title
Zirconium silicate (subacute phase)
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo (subacute phase)
Arm Type
Placebo Comparator
Arm Description
Placebo (silicified microcrystalline cellulose) randomized to mimic doses of experimental drug administered once a day (qd) prior to the morning meal for 12 days.
Intervention Type
Drug
Intervention Name(s)
Zirconium silicate (acute phase)
Other Intervention Name(s)
ZS
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Zirconium silicate (subacute phase)
Other Intervention Name(s)
ZS
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo (acute phase)
Other Intervention Name(s)
Silicified microcrystalline cellulose
Intervention Description
Randomized to mimic doses of experimental drug administered 3 times (tid) daily with meals for 48 hours during the acute phase.
Intervention Type
Drug
Intervention Name(s)
Placebo ( subacute phase)
Other Intervention Name(s)
Silicified microcrystalline cellulose
Intervention Description
Randomized to mimic doses of experimental drug administered once a day prior to the morning meal for 12 days during the subacute phase.
Primary Outcome Measure Information:
Title
Exponential Rate of Change in Serum Potassium (S-K) Levels During the Initial 48 Hours of Study Drug Treatment.
Time Frame
Through 48 hours acute phase
Title
Exponential Rate of Change in S-K Levels in the Subacute Phase.
Time Frame
Through 12 days subacute phase (Day 3 through Day 15)
Secondary Outcome Measure Information:
Title
Percentage of Subjects Who Achieve Normalization in S-K Levels After 48 Hours of Treatment
Time Frame
Through 48 hours acute phase
Title
Mean Change From Baseline in S-K at All Time Points Acute Phase
Description
Mean change from baseline in S-K at all time points over initial 48 hours
Time Frame
Through 48 hours acute phase. In particular, at Baseline; 1, 2, 4 hour Post 1st Dose on Study Day 1; 0 hour Pre-dose, 1, 4 hour Post 1st Dose on Study Day 2; and 0 hour Pre-dose on Study Day 3.
Title
Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase
Description
Mean percent change from baseline in S-K at all time points over initial 48 hours
Time Frame
Through 48 hours acute phase. In particular, 1, 2, 4 hour Post 1st Dose on Study Day 1; 0 hour Pre-dose, 1, 4 hour Post 1st Dose on Study Day 2; and 0 hour Pre-dose on Study Day 3.
Title
Time Subjects Remain Normokalemic (Subacute Phase)
Description
Time (number of days) subjects remain normokalemic (3.5 - 5.0 mmol/l) subacute phase
Time Frame
Through 18 days (12 days treatment, 6 days follow-up) of subacute phase
Title
Percentage of Subjects Within Each Treatment Group Who Retained Normal S-K Values at End of Subacute Phase
Description
Percentage of subjects within each treatment group who retained normal S-K values (values between 3.5-5.0 mmol/L) at end of subacute phase
Time Frame
Through 18 days of subacute phase (12 days treatment, 6 days follow-up)
Title
Mean Change From Subacute Baseline in Serum Potassium at All Time Points.
Description
Mean change from subacute baseline in serum potassium at all time points during subacute phase
Time Frame
Through 18 days of subacute phase (12 days treatment, 6 days follow-up)
Title
Mean Percent Change From Subacute Baseline in Serum Potassium at All Time Points.
Description
Mean percent change from subacute baseline in serum potassium at all time points during subacute phase
Time Frame
Through 18 days of subacute phase (12 days treatment, 6 days follow-up)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of written informed consent. Over 18 years of age. Mean i-STAT potassium values between 5.0 - 6.5 mmol/l inclusive, at screening (Study Day 0). Ability to have repeated blood draws or effective venous catheterization. Women of childbearing potential must be practicing a highly effective method of birth control. Exclusion Criteria: Pseudohyperkalemia signs and symptoms, such as excessive fist clinching hemolyzed blood specimen, severe leukocytosis or thrombocytosis. Subjects treated with lactulose, xifaxan or other nonabsorbed antibiotics for hyperammonemia within the last 7 days. Subjects treated with resins (such as Sevelamer acetate or Sodium polystyrene sulfonate [SPS; e.g. Kayexalate®]), calcium acetate, calcium carbonate, or lanthanum carbonate, within the last 7 days. Subjects with a life expectancy of less than 3 months. Subjects who are HIV positive. Subjects who are severely physically or mentally incapacitated and who in the opinion of investigator are unable to perform the subjects' tasks associated with the protocol. Women who are pregnant, lactating, or planning to become pregnant. Subjects with Ketoacidosis/Acidemia. Presence of any condition which, in the opinion of the investigator, places the subject at undue risk or potentially jeopardizes the quality of the data to be generated. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof. Previous treatment with ZS Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry. Subjects with cardiac arrhythmias that require immediate treatment. Insulin-dependent diabetes mellitus Subjects on dialysis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henrik Rasmussen, MD
Organizational Affiliation
ZS Pharma, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Pinnacle Research Group
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
Saadat Ansari Internal Medicine
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35801
Country
United States
Facility Name
Aspire Clinical Studies, LLC
City
Glendale
State/Province
Arizona
ZIP/Postal Code
85301
Country
United States
Facility Name
Southwest Clinical Research Institute
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85284
Country
United States
Facility Name
California Institute of Renal Research
City
Chula Vista
State/Province
California
ZIP/Postal Code
91910
Country
United States
Facility Name
Torrance Clinical Research
City
Lomita
State/Province
California
ZIP/Postal Code
90717
Country
United States
Facility Name
Academic Medical Research Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90022
Country
United States
Facility Name
Mohammad Ismail, Inc
City
Paramount
State/Province
California
ZIP/Postal Code
90723
Country
United States
Facility Name
Apex Research of Riverside
City
Riverside
State/Province
California
ZIP/Postal Code
92505
Country
United States
Facility Name
Capital Nephrology Clinical Group
City
Sacramento
State/Province
California
ZIP/Postal Code
95825
Country
United States
Facility Name
Pikes Peak Nephrology Associates
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80909
Country
United States
Facility Name
Denver Nephrologists, PC
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
Facility Name
Nephrology and Hypertension Associates
City
Middlebury
State/Province
Connecticut
ZIP/Postal Code
06762
Country
United States
Facility Name
JEM Research Institute
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Facility Name
Clinical Research of Brandon
City
Brandon
State/Province
Florida
ZIP/Postal Code
33511
Country
United States
Facility Name
Meridien Research
City
Brooksville
State/Province
Florida
ZIP/Postal Code
34601
Country
United States
Facility Name
Riverside Clinical Research
City
Edgewater
State/Province
Florida
ZIP/Postal Code
32123
Country
United States
Facility Name
Endocrinology of Central Florida
City
Lake Mary
State/Province
Florida
ZIP/Postal Code
32746
Country
United States
Facility Name
Meridien Research
City
Lakeland
State/Province
Florida
ZIP/Postal Code
33805
Country
United States
Facility Name
San Marcus Research Clinic
City
Miami
State/Province
Florida
ZIP/Postal Code
33015
Country
United States
Facility Name
Medical Consulting Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
Elite Research Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33169
Country
United States
Facility Name
Prevention & Strengthening Solutions, Inc
City
Miramar
State/Province
Florida
ZIP/Postal Code
33023
Country
United States
Facility Name
PCCC of Volusia
City
New Smyrna
State/Province
Florida
ZIP/Postal Code
32168
Country
United States
Facility Name
Meridien Research
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33709
Country
United States
Facility Name
Lakeview Medical Research
City
Summerfield
State/Province
Florida
ZIP/Postal Code
34491
Country
United States
Facility Name
Clinical Research Trials of Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
Metabolic Research Institute
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
Facility Name
Research by Design
City
Evergreen Park
State/Province
Illinois
ZIP/Postal Code
60805
Country
United States
Facility Name
Professional Research Network of Kansas, LLC
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67213
Country
United States
Facility Name
Washington Nephrology Associates
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20814
Country
United States
Facility Name
Nephrology Center DBA, Paragon Health PC
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
The Center for Clinical Trials
City
Biloxi
State/Province
Mississippi
ZIP/Postal Code
39531
Country
United States
Facility Name
Clinical Research Consultants, LLC
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
United Medical Associates
City
Binghamton
State/Province
New York
ZIP/Postal Code
13903
Country
United States
Facility Name
Life Medi-Research and Management
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11206
Country
United States
Facility Name
Doylestown Hospital Medical Research
City
Doylestown
State/Province
Pennsylvania
ZIP/Postal Code
18901
Country
United States
Facility Name
South Carolina Nephrology & Hypertension
City
Orangeburg
State/Province
South Carolina
ZIP/Postal Code
29118
Country
United States
Facility Name
Carolina Diabetes and Kidney Center
City
Sumter
State/Province
South Carolina
ZIP/Postal Code
29150
Country
United States
Facility Name
Southwest Houston Research, Ltd
City
Houston
State/Province
Texas
ZIP/Postal Code
77099
Country
United States
Facility Name
Clinical Advancement Center, PLLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Southern Utah Kidney and Hypertension Center
City
Saint George
State/Province
Utah
ZIP/Postal Code
84770
Country
United States
Facility Name
Renal Research
City
Gosford
State/Province
New South Wales
ZIP/Postal Code
02250
Country
Australia
Facility Name
Melbourne Renal Research Group
City
Reservoir
State/Province
Victoria
ZIP/Postal Code
03073
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
32588430
Citation
Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020 Jun 26;6(6):CD013165. doi: 10.1002/14651858.CD013165.pub2.
Results Reference
derived
PubMed Identifier
31791288
Citation
Amin AN, Menoyo J, Singh B, Kim CS. Efficacy and safety of sodium zirconium cyclosilicate in patients with baseline serum potassium level >/= 5.5 mmol/L: pooled analysis from two phase 3 trials. BMC Nephrol. 2019 Dec 2;20(1):440. doi: 10.1186/s12882-019-1611-8.
Results Reference
derived
PubMed Identifier
29728199
Citation
Friedman PA, Scott CG, Bailey K, Baumann NA, Albert D, Attia ZI, Ladewig DJ, Yasin O, Dillon JJ, Singh B. Errors of Classification With Potassium Blood Testing: The Variability and Repeatability of Critical Clinical Tests. Mayo Clin Proc. 2018 May;93(5):566-572. doi: 10.1016/j.mayocp.2018.03.013.
Results Reference
derived
PubMed Identifier
25415807
Citation
Packham DK, Rasmussen HS, Lavin PT, El-Shahawy MA, Roger SD, Block G, Qunibi W, Pergola P, Singh B. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015 Jan 15;372(3):222-31. doi: 10.1056/NEJMoa1411487. Epub 2014 Nov 21.
Results Reference
derived

Learn more about this trial

Safety & Efficacy of Zirconium Silicate in Mild to Moderate Hyperkalemia

We'll reach out to this number within 24 hrs