Clinical trial NCT02107092: Open-label Safety & Efficacy of ZS (Sodium Zirconium Cyclosilicate)10g qd to Extend Study ZS-004 in Hyperkalemia.
Official title: 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.]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperkalemia
Lead sponsor: ZS Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2014-04-08
Enrollment: 123
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: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L
timeFrame: 11 months
Secondary outcomes:
measure: Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L
timeFrame: 11 months
Other outcomes:
Locations:
city: Anniston
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Scottsboro
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Tempe
country: United States
state: Arizona
city: Hawaiian Gardens
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: Atlantis
country: United States
state: Florida
city: Bradenton
country: United States
state: Florida
city: Brandon
country: United States
state: Florida
city: Brooksville
country: United States
state: Florida
city: DeLand
country: United States
state: Florida
city: Edgewater
country: United States
state: Florida
city: Miami 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: Ocala
country: United States
state: Florida
city: Summerfield
country: United States
state: Florida
city: Tampa
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: Decatur
country: United States
state: Georgia
city: Evergreen Park
country: United States
state: Illinois
city: Joliet
country: United States
state: Illinois
city: Shreveport
country: United States
state: Louisiana
city: Auburn
country: United States
state: Maine
city: Chesterfield
country: United States
state: Michigan
city: Kansas City
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Flushing
country: United States
state: New York
city: Altoona
country: United States
state: Pennsylvania
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: 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: Meyerspark
country: South Africa
city: Port Elizabeth
country: South Africa
city: Somerset West
country: South Africa
Study officials:
affiliation: ZS Pharma, Inc.
name: Henrik Rasmussen, MD, PhD
role: STUDY_CHAIR
References: