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

Hyperkalemia Clinical Trial

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.]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02107092
• Other study ID #: ZS-004E
• Status: Completed
• Phase: Phase 3
• Start date: May 31, 2014
• Est. completion date: August 31, 2015

Study information

• Verified date: July 2018
• Source: ZS Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: August 31, 2015
• Est. primary completion date: July 31, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hyperkalemia

Intervention

Drug:
• Sodium Zirconium Cyclosilicate
Oral 10g once daily with breakfast for 11 months.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
ZS Pharma, Inc.

Countries where clinical trial is conducted

United States,  Australia,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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