open-label safety & efficacy of zs (sodium zirconium cyclosilicate)10g qd to extend study zs-004 in hyperkalemia.

Conditions: Hyperkalemia

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.

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.