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Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months

Primary Purpose

Hyperkalemia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Sodium Zirconium Cyclosilicate
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.
  • Two consecutive i STAT potassium values, measured 60 (+/- 15) minutes apart, both >/= 5.1 mmol/L and measured within 1 day before the first dose of ZS on Acute Phase Study Day 1.
  • Ability to have repeated blood draws or effective venous catheterization.
  • Women of childbearing potential must be using 2 forms of medically acceptable contraception (at least 1 barrier method) and have a negative pregnancy test at Acute Phase Study Day 1. Women who are surgically sterile or those who are postmenopausal for at least 2 years are not considered to be of childbearing potential.
  • Controlled diabetic subjects.

Exclusion Criteria:

  • Pseudohyperkalemia signs and symptoms, such as hemolyzed blood specimen due to excessive fist clenching to make veins prominent, difficult or traumatic venipuncture, or history of severe leukocytosis or thrombocytosis.
  • Subjects treated with lactulose, rifaximin, or other non-absorbed antibiotics for hyperammonemia within 7 days prior to first dose of ZS on Acute Phase Study Day 1.
  • Subjects treated with sodium polystyrene sulfonate (SPS; eg, Kayexalate®) or calcium polystyrene sulfonate (eg, Resonium®) within 3 days prior to first dose of ZS on Acute Phase Study Day 1.
  • Subjects with a life expectancy of less than 12 months.
  • 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 diabetic ketoacidosis.
  • 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.
  • 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.
  • Subjects on dialysis.
  • Subjects randomized into the previous ZS-002, ZS-003, ZS-004, or ZS-004E studies.
  • Documented GFR <15 mL/min within 90 days prior to study entry.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sodium Zirconium Cyclosilicate

Arm Description

Outcomes

Primary Outcome Measures

Percent of Participants With Restoration of Normal Serum Potassium (S-K) Values (3.5 to 5.0 mmol/L, Inclusive) at the End of the Acute Phase
Percentage of subjects with S-K values between 3.5 and 5.0 mmol/L, inclusive at the end of the Acute Phase - ITT Population
Percentage of Participants With Mean S-K Values ≤ 5.1 mmol/L During Extended Dosing Phase Days 85 to 365
Percentage of subjects with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase - ITT Population

Secondary Outcome Measures

Proportion of Subjects With Mean S-K Between 3.5 and 5.5 mmol/L, Inclusive Months 3 to 12
Proportion of Subjects with mean S-K between 3.5 and 5.5 mmol/L during Extended Dosing Phase - ITT Population
Mean S-K Levels Months 3 to 12, Months 6 to 9, and Months 9 to 12.
Mean S-K levels months 3 to 12(EP Days 85, 113, 141, 176, 211, 239, 267, 295, 330, 365 and EOS),months 6 to 9, and months 9 to 12.

Full Information

First Posted
June 11, 2014
Last Updated
May 29, 2018
Sponsor
ZS Pharma, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02163499
Brief Title
Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months
Official Title
Multicenter, Multi-Dose, Open-Label Maintenance of Long-Term Safety and Efficacy of Sodium Zirconium Cyclosilicate (ZS) in Hyperkalemia
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
June 30, 2014 (Actual)
Primary Completion Date
November 30, 2016 (Actual)
Study Completion Date
November 30, 2016 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The Open-Label Maintenance Study contains an Acute Phase, in which subjects will be dosed with ZS 10 g three times daily (tid) for 24 to 72 hours, followed by a long-term Maintenance Phase.
Detailed Description
Subjects with 2 consecutive i STAT potassium values 5.1 mmol/L will enter the Acute Phase and receive ZS 10 g tid for 24 to 72 hours, depending on potassium values. Once normokalemia (i STAT potassium between 3.5 and 5.0 mmol/L, inclusive) is restored (whether after 24, 48 or 72 hours), subjects will be enrolled in the Maintenance Phase to be dosed with ZS at a starting dose of 5 g qd. Potassium (i STAT and central laboratory) will be measured weekly throughout the first month of study and every 4 weeks thereafter through Month 12. During the Maintenance Phase, the ZS dose may be increased or decreased in increments/decrements of 5 g qd up to a maximum of 15 g qd or a minimum of 5 g every other day based on i STAT potassium measurements as outlined below: • > 5.0 mmol/L while receiving 5 g qd or 5 g every other day or > 5.5 mmol/L while receiving 10 g qd: increase ZS dose in 5 g qd increments to a maximum dose of 15 g qd .• Between 3.0 and 3.4 mmol/L, inclusive: decrease ZS dose in 5 g qd decrements to a minimum dose of 5 g every other day; if a subject's i STAT potassium value remains between 3.0 and 3.4 mmol/L, inclusive, on the ZS 5 g every other day dose, the subject will be withdrawn from the study and receive standard of care treatment. There is no limit to the number of dose titrations allowed. Subjects will receive up to 12 months of treatment with open-label ZS.

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
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
751 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sodium Zirconium Cyclosilicate
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Sodium Zirconium Cyclosilicate
Other Intervention Name(s)
ZS
Intervention Description
Acute Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) for 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) based on i-STAT potassium measurements up to 12 months.
Primary Outcome Measure Information:
Title
Percent of Participants With Restoration of Normal Serum Potassium (S-K) Values (3.5 to 5.0 mmol/L, Inclusive) at the End of the Acute Phase
Description
Percentage of subjects with S-K values between 3.5 and 5.0 mmol/L, inclusive at the end of the Acute Phase - ITT Population
Time Frame
72 Hours
Title
Percentage of Participants With Mean S-K Values ≤ 5.1 mmol/L During Extended Dosing Phase Days 85 to 365
Description
Percentage of subjects with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase - ITT Population
Time Frame
Study Days 85 to 365
Secondary Outcome Measure Information:
Title
Proportion of Subjects With Mean S-K Between 3.5 and 5.5 mmol/L, Inclusive Months 3 to 12
Description
Proportion of Subjects with mean S-K between 3.5 and 5.5 mmol/L during Extended Dosing Phase - ITT Population
Time Frame
Study Days 85 to 365
Title
Mean S-K Levels Months 3 to 12, Months 6 to 9, and Months 9 to 12.
Description
Mean S-K levels months 3 to 12(EP Days 85, 113, 141, 176, 211, 239, 267, 295, 330, 365 and EOS),months 6 to 9, and months 9 to 12.
Time Frame
Study days 85 to 365

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. Two consecutive i STAT potassium values, measured 60 (+/- 15) minutes apart, both >/= 5.1 mmol/L and measured within 1 day before the first dose of ZS on Acute Phase Study Day 1. Ability to have repeated blood draws or effective venous catheterization. Women of childbearing potential must be using 2 forms of medically acceptable contraception (at least 1 barrier method) and have a negative pregnancy test at Acute Phase Study Day 1. Women who are surgically sterile or those who are postmenopausal for at least 2 years are not considered to be of childbearing potential. Controlled diabetic subjects. Exclusion Criteria: Pseudohyperkalemia signs and symptoms, such as hemolyzed blood specimen due to excessive fist clenching to make veins prominent, difficult or traumatic venipuncture, or history of severe leukocytosis or thrombocytosis. Subjects treated with lactulose, rifaximin, or other non-absorbed antibiotics for hyperammonemia within 7 days prior to first dose of ZS on Acute Phase Study Day 1. Subjects treated with sodium polystyrene sulfonate (SPS; eg, Kayexalate®) or calcium polystyrene sulfonate (eg, Resonium®) within 3 days prior to first dose of ZS on Acute Phase Study Day 1. Subjects with a life expectancy of less than 12 months. 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 diabetic ketoacidosis. 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. 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. Subjects on dialysis. Subjects randomized into the previous ZS-002, ZS-003, ZS-004, or ZS-004E studies. Documented GFR <15 mL/min within 90 days prior to study entry.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henrik Rasmussen, MD, PhD
Organizational Affiliation
ZS Pharma, Inc.
Official's Role
Study Chair
Facility Information:
City
Scottsboro
State/Province
Alabama
ZIP/Postal Code
35768
Country
United States
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85284
Country
United States
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
City
Chula Vista
State/Province
California
ZIP/Postal Code
90717
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90022
Country
United States
City
Paramount
State/Province
California
ZIP/Postal Code
90723
Country
United States
City
Riverside
State/Province
California
ZIP/Postal Code
92505
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95825
Country
United States
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
City
Brandon
State/Province
Florida
ZIP/Postal Code
33511
Country
United States
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
City
Hudson
State/Province
Florida
ZIP/Postal Code
34667
Country
United States
City
Lauderdale Lakes
State/Province
Florida
ZIP/Postal Code
33313
Country
United States
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33018
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33015
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
City
New Smyrna Beach
State/Province
Florida
ZIP/Postal Code
32168
Country
United States
City
New Smyrna
State/Province
Florida
ZIP/Postal Code
32168
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
City
Winter Park
State/Province
Florida
ZIP/Postal Code
32789
Country
United States
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31901
Country
United States
City
Evergreen Park
State/Province
Illinois
ZIP/Postal Code
60805
Country
United States
City
Joliet
State/Province
Illinois
ZIP/Postal Code
60435
Country
United States
City
Paducah
State/Province
Kentucky
ZIP/Postal Code
42003
Country
United States
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71101
Country
United States
City
Chesterfield
State/Province
Michigan
ZIP/Postal Code
48047
Country
United States
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64411
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
City
Orangeburg
State/Province
South Carolina
ZIP/Postal Code
29118
Country
United States
City
Sumter
State/Province
South Carolina
ZIP/Postal Code
29150
Country
United States
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37408
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
City
Saint George
State/Province
Utah
ZIP/Postal Code
84770
Country
United States
City
Gosford
State/Province
New South Wales
ZIP/Postal Code
2250
Country
Australia
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3073
Country
Australia
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
City
Berlin
ZIP/Postal Code
13353
Country
Germany
City
Stuttgart
ZIP/Postal Code
70376
Country
Germany
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
City
Lasi
ZIP/Postal Code
700503
Country
Romania
City
Cape Town
ZIP/Postal Code
7925
Country
South Africa
City
Meyerspark
Country
South Africa
City
Port Elizabeth
ZIP/Postal Code
6001
Country
South Africa
City
Somerset West
ZIP/Postal Code
7130
Country
South Africa
City
Leicester
ZIP/Postal Code
LE1 9HN
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32030422
Citation
Roger SD, Lavin PT, Lerma EV, McCullough PA, Butler J, Spinowitz BS, von Haehling S, Kosiborod M, Zhao J, Fishbane S, Packham DK. Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study. Nephrol Dial Transplant. 2021 Jan 1;36(1):137-150. doi: 10.1093/ndt/gfz285.
Results Reference
derived

Learn more about this trial

Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months

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