Clinical trial NCT01866709: Safety and Efficacy of Sodium Polystyrene Sulfonate in Hyperkalemia
Official title: A Phase 4, Single-center, Prospective, Double-blind, Placebo-controlled, Randomized Study to Investigate the Safety and Efficacy of Sodium Polystyrene Sulfonate (SPS) in Subjects With Hyperkalemia.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hyperkalemia
Lead sponsor: ZS Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2013-05-31
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: It is hypothesized that SPS is more effective than placebo control (alternative hypothesis) in lowering i-STAT potassium levels in subjects with i-STAT potassium levels between 5.0 - 6.5 mmol/l versus no difference between SPS and placebo control (null hypothesis).

Detailed description: Subjects with mild to moderate hyperkalemia (i-STAT potassium levels between 5.0-6.5 mmol/l, inclusive) will be randomized 1:1 in a double-blind fashion to receive placebo or SPS (15g), administered tid with meals for 48 hours. Subjects will come back to the clinic on Study Day 9 for an End of Study (EOS) visit. Adverse experiences will be recorded.

Blood potassium levels will be evaluated by both i-STAT and the Local Laboratory prior to the first dose on Study Days 1 and 2, 1, 2, and 4 hours after the first dose on Study Day 1, 1 and 4 hours after the first dose on Study Day 2 and prior to breakfast on Study Day 3, after 48 hours of treatment.

Subjects who have i-STAT potassium levels \> 6.5 mmol/l on Study Day 1 at the 4 hour post Dose 1 time point will be withdrawn from the study and will receive standard of care. If the i-STAT potassium value is between 6.1 and 6.5 mmol/l at the 4-hour post Dose 1 draw, subjects will be kept in the clinic for another 90 minutes post Dose 2 and another blood draw will be taken and an ECG will be performed. If the i-STAT potassium level is ≥ 6.2 mmol/l at this time point, the subject will be discontinued from the study and standard of care will be instituted. If the i-STAT potassium level is \< 6.2 mmol/l, and the ECG does not show any of the ECG withdrawal criteria (see below), the subject will continue in the study.

Eligibility criteria: Inclusion Criteria:

* Provision of written informed consent.
* Over 18 years of age.
* Mean i-STAT potassium values between 5.0 - 6.5 mmol/l inclusive, at screening (Study Day 0).
* Previous participation in Clinical ZS-002 or ZS-003 protocol(s). However, subjects cannot be enrolled in this study until at least 30 days have elapsed from their last dose in study ZS-003.
* Ability to have repeated blood draws or effective venous catheterization.
* Women of childbearing potential must be using two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at screening.

Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of child-bearing potential.

Exclusion Criteria:

* Pseudohyperkalemia signs and symptoms, such as excessive fist clenching hemolyzed blood specimen, severe leukocytosis or thrombocytosis.
* Subjects treated with lactulose, Xifaxan or other non-absorbed antibiotics for hyperammonemia within the last 7 days.
* Subjects treated with resins (such as Sevelamer acetate), calcium acetate, calcium carbonate, or lanthanum carbonate, within the last 7 days.
* Subjects treated with Sodium Polystyrene Sulfonate (SPS; e.g. Kayexalate®) or ZS (microporous, fractionated, protonated zirconium silicate) within the last 30 days.
* Subjects with a life expectancy of less than 3 months.
* Subjects who are HIV positive.
* 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.
* Previous treatment with SPS.
* 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 insulin where a stable dose has not yet been established.\*
* Subjects on dialysis. \* Subjects on stable insulin or insulin analogues can be enrolled. Subjects who have been on the same insulin dose and regimen for \> 14 days are considered stable. Whenever possible, all blood draws collected prior to meals should be collected prior to insulin/insulin analogue treatment.

Primary outcomes:
measure: Change in Serum Potassium Levels From Baseline After Administration of Sodium Polystyrene Sulfonate (SPS) Three Times a Day Without Co-administration of Sorbitol; Determine Incidence of Adverse Events.
timeFrame: First 48 hours
Secondary outcomes:
measure: Change in Serum Sodium, Magnesium, Calcium Levels From Baseline After Administration of SPS.
timeFrame: First 48 hours
Other outcomes:
Locations:
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
Study officials:
affiliation: ZS Pharma, Inc.
name: Henrik Rasmussen, MD
role: STUDY_CHAIR
References: