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

Phase 3

Completed

• Conditions: Hyperkalemia
• Interventions: Drug: Sodium Zirconium Cyclosilicate

• Registration Number: NCT02163499
• Lead Sponsor: ZS Pharma, Inc.

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potassium value remains between 3.0 and 3.4 mmol/L, inclusive, on the ZS 5 g every other day dose, the subject will be withdrawn from the study and receive standard of care treatment.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.

Study Timeline

• Study First Submitted: 2014-06-11
• Study First Submitted QC: 2014-06-12
• Study First Posted: 2014-06-13
• Study Start: 2014-06-30
• Primary Completion: 2016-11-30
• Study Completion: 2016-11-30
• Results First Submitted: 2018-03-28
• Status Verified: 2018-05
• Results First Submitted QC: 2018-05-29
• Last Update Submitted: 2018-05-29
• Results First Posted: 2018-06-27
• Last Update Posted: 2018-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 751

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sodium Zirconium Cyclosilicate	Sodium Zirconium Cyclosilicate	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Mean S-K Values ≤ 5.1 mmol/L During Extended Dosing Phase Days 85 to 365	Study Days 85 to 365	Percentage of subjects with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase - ITT Population
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	72 Hours	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

Secondary Outcome Measures

Name	Time	Method
Proportion of Subjects With Mean S-K Between 3.5 and 5.5 mmol/L, Inclusive Months 3 to 12	Study Days 85 to 365	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.	Study days 85 to 365	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.