Safety and Efficacy of Sodium Polystyrene Sulfonate in Hyperkalemia

• ClinicalTrials.gov Identifier: NCT01866709
• Recruitment Status: Terminated
• First Posted: May 31, 2013
• Results First Posted: September 3, 2014
• Last Update Posted: September 3, 2014
• Sponsor: ZS Pharma, Inc.
• Information provided by (Responsible Party): ZS Pharma, Inc.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Hyperkalemia	Drug: Sodium polystyrene sulfonate; Drug: Silicified microcrystalline cellulose	Phase 4

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 6.5 mmol/l on Study Day 1 at the 4 hour post Dose 1 time point will be withdrawn from the study and will receive standard of care.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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• 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 Start Date: May 2013
• Actual Primary Completion Date: July 2013
• Actual Study Completion Date: August 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Sodium Polystyrene Sulfonate; Oral suspension in water of 15g sodium polystyrene sulfonate administered three times (tid) daily for 48 hours without co-administration of Sorbitol.	Drug: Sodium polystyrene sulfonate; Oral suspension in water of 15g sodium polystyrene sulfonate administered three times (tid) daily for 48 hours without co-administration of Sorbitol.; Other Name: SPS
Placebo Comparator: Silicified microcrystalline cellulose; Oral suspension of placebo blended with pigment to have the same appearance, taste, odor and mode of administration as SPS.	Drug: Silicified microcrystalline cellulose; Oral suspension in water of placebo administered three times (tid) daily for 48 hours.; Other Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: First 48 hours ]
   To perform a controlled evaluation of the safety and efficacy of 15g of SPS administered 3 times daily for 48 hours (6 doses) in patients with hyperkalemia (serum potassium levels between 5.0 - 6.5 mmol/l) at baseline.

Secondary Outcome Measures :

1. Change in Serum Sodium, Magnesium, Calcium Levels From Baseline After Administration of SPS. [ Time Frame: First 48 hours ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

Riverside Clinical Research

Edgewater, Florida, United States, 32132

Sponsors and Collaborators

ZS Pharma, Inc.

Investigators

• Study Chair: Henrik Rasmussen, MD; ZS Pharma, Inc.

More Information

• Responsible Party: ZS Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT01866709
• Other Study ID Numbers: SPS-001
• First Posted: May 31, 2013
• Results First Posted: September 3, 2014
• Last Update Posted: September 3, 2014
• Last Verified: August 2014

Additional relevant MeSH terms:

Hyperkalemia; Water-Electrolyte Imbalance; Metabolic Diseases; Polystyrene sulfonic acid; Chelating Agents; Sequestering Agents; Molecular Mechanisms of Pharmacological Action