Safety and Efficacy of Sodium Polystyrene Sulfonate in Hyperkalemia

This study has been terminated.
(Risk/benefit determinations in three subjects on SPS, study blind was broken.)
Sponsor:
Information provided by (Responsible Party):
ZS Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01866709
First received: May 28, 2013
Last updated: August 15, 2013
Last verified: August 2013
  Purpose

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 Intervention Phase
Hyperkalemia
Drug: Sodium polystyrene sulfonate
Drug: Silicified microcrystalline cellulose
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by ZS Pharma, Inc.:

Primary Outcome Measures:
  • Change in serum potassium levels from baseline after administration of sodium polystyrene sulfonate (SPS) three times a day. [ Time Frame: First 48 hours ] [ Designated as safety issue: Yes ]
    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:
  • Change in serum sodium, magnesium, calcium levels from baseline after administration of SPS. [ Time Frame: First 48 hours ] [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: May 2013
Estimated Study Completion Date: December 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sodium Polystyrene Sulfonate
Oral suspension in water of 15g sodium polystyrene sulfonate administered three times (tid) daily for 48 hours.
Drug: Sodium polystyrene sulfonate
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
Other Name: Placebo

Detailed Description:

A total of 46 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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01866709

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

No publications provided

Responsible Party: ZS Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01866709     History of Changes
Other Study ID Numbers: SPS-001
Study First Received: May 28, 2013
Last Updated: August 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hyperkalemia
Water-Electrolyte Imbalance
Metabolic Diseases
Polystyrene sulfonic acid
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014