Clinical trial NCT02163499: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperkalemia
Lead sponsor: ZS Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2014-06-13
Enrollment: 751
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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potassium value remains between 3.0 and 3.4 mmol/L, inclusive, on the ZS 5 g every other day dose, the subject will be withdrawn from the study and receive standard of care treatment.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

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.

Primary outcomes:
measure: 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
timeFrame: 72 Hours
measure: Percentage of Participants With Mean S-K Values ≤ 5.1 mmol/L During Extended Dosing Phase Days 85 to 365
timeFrame: Study Days 85 to 365
Secondary outcomes:
measure: Proportion of Subjects With Mean S-K Between 3.5 and 5.5 mmol/L, Inclusive Months 3 to 12
timeFrame: Study Days 85 to 365
measure: Mean S-K Levels Months 3 to 12, Months 6 to 9, and Months 9 to 12.
timeFrame: Study days 85 to 365
Other outcomes:
Locations:
city: Scottsboro
country: United States
state: Alabama
city: Tempe
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Chula Vista
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Paramount
country: United States
state: California
city: Riverside
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Whittier
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Brandon
country: United States
state: Florida
city: DeLand
country: United States
state: Florida
city: Hudson
country: United States
state: Florida
city: Lauderdale Lakes
country: United States
state: Florida
city: Miami Lakes
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Smyrna Beach
country: United States
state: Florida
city: New Smyrna
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Columbus
country: United States
state: Georgia
city: Evergreen Park
country: United States
state: Illinois
city: Joliet
country: United States
state: Illinois
city: Paducah
country: United States
state: Kentucky
city: Shreveport
country: United States
state: Louisiana
city: Chesterfield
country: United States
state: Michigan
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Great Neck
country: United States
state: New York
city: Providence
country: United States
state: Rhode Island
city: Orangeburg
country: United States
state: South Carolina
city: Sumter
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Saint George
country: United States
state: Utah
city: Gosford
country: Australia
state: New South Wales
city: Woolloongabba
country: Australia
state: Queensland
city: Heidelberg
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Parkville
country: Australia
state: Victoria
city: Berlin
country: Germany
city: Stuttgart
country: Germany
city: Amsterdam
country: Netherlands
city: Lasi
country: Romania
city: Cape Town
country: South Africa
city: Meyerspark
country: South Africa
city: Port Elizabeth
country: South Africa
city: Somerset West
country: South Africa
city: Leicester
country: United Kingdom
Study officials:
affiliation: ZS Pharma, Inc.
name: Henrik Rasmussen, MD, PhD
role: STUDY_CHAIR
References:
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.