Open-label Safety & Efficacy of ZS (Sodium Zirconium Cyclosilicate)10g qd to Extend Study ZS-004 in Hyperkalemia.

Open-label Extension to Study ZS-004 [Phase 3 Multicenter, Multi-phase, Multi-dose, Prospective, Randomized, Double-blind, Placebo-controlled Maintenance Study of Safety Efficacy of ZS (Sodium Zirconium Cycolsilicate) in Hyperkalemia.]

Subjects who completed the Double-blind Randomized Maintenance Phase (DBRMP) Study Day 29 visit in ZS-004 (NCT 02088073) and have an i-STAT potassium value that is 3.5 to 6.2 mmol/l inclusive or who discontinued during ZS-004 due to hypo- or hyperkalemia in the DBRMP and have a mean i-STAT potassium value from two consecutive measurements at 0 and 60 minutes on Acute Phase Day 1/Maintenance Phase Day 1 that is 3.5 to 6.2 mmol/l inclusive may have the option to participate in ZS-004E (NCT 021070920). Subjects who discontinued from study ZS-004 due to any other reasons (e.g. adverse events, poor compliance, investigator decision) will not be entered into study ZS-004E. All subjects who continue into the extension study must begin dosing within two (2) days after the last dose of investigational product in ZS-004.

Study Overview

• Status: Completed
• Conditions: Hyperkalemia
• Intervention / Treatment: Drug: Sodium Zirconium Cyclosilicate

Detailed Description

All subjects with i-STAT potassium values between 3.5-5.5 mmol/l, inclusive at the ZS-004 (NCT 02088073) DBRMP Study Day 29 visit, who continue directly into the open-label extension study ZS-004E (NCT 021070920), will enter the Maintenance Phase (MP) and start on open-label ZS at a dose of 10g qd. All subjects with i-STAT potassium values > 5.5 mmol/l at the ZS-004 DBRMP Study Day 29 visit will undergo an acute treatment phase (AP) where they will receive ZS 10g three times a day (tid) for 24 (3 doses) or 48 hours (6 doses). If the subject's i-STAT potassium is between 3.5-5.0 mmol/l, inclusive after 24 (AP Study Day 2) or 48 hours (AP Study Day 3), the subject will enter the MP at a starting dose of 10g qd.

For subjects who discontinued during ZS-004 DBRMP due to hypo- or hyperkalemia baseline potassium values will be determined within 1 day of administration of the first dose in the ZS-004E extension study by taking two (2) consecutive i-STAT potassium measurements at 0 and 60 minutes (± 10 minutes). If the mean i-STAT value is between 3.5 - 5.5 mmol/l, inclusive, the subject will enter directly into the MP and receive 10g ZS qd; if the mean i-STAT potassium value is > 5.5 mmol/l, the subject will enter the AP. If i-STAT potassium values are still >5.0 mmol/l on the morning of AP Study Day 3, subjects will not enter the MP but will be referred to their normal health care provider for standard of care.

If the i-STAT potassium value increases above 5.5 mmol/l during the MP with treatment at 10g qd, the dose can be increased to15g qd. Conversely, if S-K decreases to between 3.0-3.4 mmol/l, inclusive, the dose of ZS can be decreased in 5g qd, decrements. If a subject is on a 5g qd dose and still develops blood potassium i-STAT values between 3.0 - 3.4mmol, inclusive the dose can be reduced to 5g every other day.

Subjects will receive up to 11 months of treatment with open-label ZS.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Gosford, New South Wales, Australia
  • Queensland
    • Woolloongabba, Queensland, Australia
  • Victoria
    • Heidelberg, Victoria, Australia
    • Melbourne, Victoria, Australia
    • Parkville, Victoria, Australia
• South Africa
  • Meyerspark, South Africa
  • Port Elizabeth, South Africa
  • Somerset West, South Africa
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
    • Huntsville, Alabama, United States, 35801
    • Scottsboro, Alabama, United States, 35768
  • Arizona
    • Phoenix, Arizona, United States, 85027
    • Tempe, Arizona, United States, 85284
  • California
    • Hawaiian Gardens, California, United States, 90716
    • Los Angeles, California, United States, 90022
    • Paramount, California, United States, 90723
    • Riverside, California, United States, 92505
  • Florida
    • Atlantis, Florida, United States, 33462
    • Bradenton, Florida, United States, 34208
    • Brandon, Florida, United States, 33511
    • Brooksville, Florida, United States, 34601
    • DeLand, Florida, United States, 32720
    • Edgewater, Florida, United States, 32132
    • Miami, Florida, United States, 33125
    • Miami, Florida, United States, 33015
    • Miami Lakes, Florida, United States, 33014
    • Miami Lakes, Florida, United States, 33018
    • New Smyrna Beach, Florida, United States, 32168
    • Ocala, Florida, United States, 34471
    • Summerfield, Florida, United States, 34491
    • Tampa, Florida, United States, 33607
    • Tampa, Florida, United States, 33614
    • Winter Park, Florida, United States, 32789
  • Georgia
    • Columbus, Georgia, United States, 31901
    • Decatur, Georgia, United States, 30030
  • Illinois
    • Evergreen Park, Illinois, United States, 60805
    • Joliet, Illinois, United States, 60435
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
  • Maine
    • Auburn, Maine, United States, 04210
  • Michigan
    • Chesterfield, Michigan, United States, 48047
  • Missouri
    • Kansas City, Missouri, United States, 64411
  • Nevada
    • Las Vegas, Nevada, United States, 89115
  • New York
    • Flushing, New York, United States, 11355
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
    • Sumter, South Carolina, United States, 29150
  • Tennessee
    • Chattanooga, Tennessee, United States, 37408
  • Texas
    • San Antonio, Texas, United States, 78229

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of written informed consent.
• Completed the ZS-004 DBRMP Study Day 29 visit or discontinued study ZS-004 during the DBRMP due to hypo- or hyperkalemia and able to start dosing in ZS-004E within two (2) days after the last dose of Investigational product in ZS-004.
• Subject must have an i-STAT potassium value that is 3.5 to 6.2 mmol/l inclusive at the ZS-004 DBRMP Study Day 29 visit or a mean i-STAT potassium value from two consecutive measurements at 0 and 60 minutes on Acute Phase Day 1/Maintenance Phase Day 1 that is 3.5 to 6.2 mmol/l inclusive if the subject discontinued study ZS-004 during the DBRMP due to hypo- or hyperkalemia .

Exclusion Criteria:

• Pseudohyperkalemia signs and symptoms, such as excessive fist clenching hemolyzed blood specimen, history of severe leukocytosis or thrombocytosis.
• Subjects who received alternative treatment for hyperkalemia while participating in study ZS-004.
• Subjects with a life expectancy of less than 3 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 other than ZS 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium Zirconium Cyclosilicate; Open label oral administration of sodium zirconium cyclosilicate 10g once daily for 11 months.	Drug: Sodium Zirconium Cyclosilicate; Oral 10g once daily with breakfast for 11 months.; Other Names: ZS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L	The proportions of subjects with average serum potassium (S-K) values ≤ 5.1 mmol/L during Extended Dosing Study Days 8 to 337, inclusive	11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L	The proportions of subjects with average S-K values ≤ 5.5 mmol/L during Extended Dosing Study Days 8 to 337, inclusive	11 months

Collaborators and Investigators

• Sponsor: ZS Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2014
• Primary Completion (Actual): July 31, 2015
• Study Completion (Actual): August 31, 2015

Study Registration Dates

• First Submitted: April 3, 2014
• First Submitted That Met QC Criteria: April 3, 2014
• First Posted (Estimate): April 8, 2014

Study Record Updates

• Last Update Posted (Actual): August 15, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyperkalemia
• Other Study ID Numbers: ZS-004E

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No