Safety & Efficacy of Zirconium Silicate in Mild to Moderate Hyperkalemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ZS Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01737697
First received: November 19, 2012
Last updated: November 15, 2013
Last verified: November 2013
  Purpose

Acute Phase: It is hypothesized that ZS (zirconium silicate) is more effective than placebo control (alternative hypothesis) in lowering S-K levels in subjects with S-K between 5.0 - 6.5 mmol/l versus no difference between ZS and placebo control (null hypothesis).

Subacute Phase (randomized withdrawal): It is hypothesized that ZS once daily is more effective than placebo control (alternative hypotheses) in maintaining normokalemic levels (3.5 - 4.9 mmol/l) among subjects completing the Acute Phase versus no difference between each ZS dose and respective placebo controls (null hypotheses).


Condition Intervention Phase
Hyperkalemia
Drug: Zirconium silicate (acute phase)
Drug: Zirconium silicate (subacute phase)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Multicenter, Two-phase, Multi-dose, Prospective, Randomized, Double-blind, Placebo-Controlled Study of Safety and Efficacy of Microporous, Fractionated, Protonated Zirconium Silicate in Mild to Moderate 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 zirconium silicate 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 four (4) different doses of ZS administered 3 times daily for 48 hours in the Acute Phase for patients with mild to moderate hyperkalemia (potassium level between 5.0-6.5 mmol/l as determined by i-STAT) at baseline.


Secondary Outcome Measures:
  • Change in serum potassium levels from baseline after administration of zirconium silicate once a day for patients who first completed 48 hours of dosing tid. [ Time Frame: additional 12 days ] [ Designated as safety issue: Yes ]
    To perform a controlled evaluation of the safety and efficacy of four different doses of ZS administered once daily for 12 additional days in a subsequent Subacute Phase for patients completing the Acute Phase and achieving potassium levels within the normal range (3.5 - 4.9 mmol/l, as determined by i-STAT).


Other Outcome Measures:
  • Change in serum sodium, magnesium, calcium and blood urea nitrogen (BUN) from baseline after administration of zirconium silicate three times a day. [ Time Frame: first 48 hours ] [ Designated as safety issue: Yes ]

Enrollment: 750
Study Start Date: November 2012
Study Completion Date: November 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zirconium silicate (acute phase)
Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered 3 times (tid) daily with meals for 48 hours.
Drug: Zirconium silicate (acute phase)
Other Name: ZS
Placebo Comparator: Silicified microcrystalline cellulose
Randomized to mimic doses of experimental drug administered 3 times (tid) daily with meals.
Drug: Zirconium silicate (acute phase)
Other Name: ZS
Experimental: Zirconium silicate (subacute phase)
Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered once a day prior to the morning meal for 12 days.
Drug: Zirconium silicate (subacute phase)
Other Name: ZS
Placebo Comparator: Silicified microcrystalline cellulose-qd
Randomized to mimic doses of experimental drug administered once a day prior to the morning meal for 12 days.
Drug: Zirconium silicate (subacute phase)
Other Name: ZS

Detailed Description:

A total of 750 subjects with mild to moderate hyperkalemia (i- STAT potassium levels between 5.0-6.5 mmol/l, inclusive) will be enrolled in the study where they, in a double-blind fashion, will be randomized 1:1:1:1:1 to receive one of four (4) doses of ZS (1.25g, 2.5g, 5g, and 10g) or placebo control, administered 3 times daily (tid) with meals for the initial 48 hours (Acute Phase), followed by a Subacute Phase (randomized withdrawal) during which patients treated with active doses in the Acute Phase, who achieve normokalemia (i-STAT potassium values 3.5 to 4.9 mmol/l, inclusive) will be randomized to 12 days of subacute, once a day (qd) dosing. There will be a one-time randomization to assign the Acute Phase treatment and the Subacute Phase treatment. The Subacute Phase will include subjects who became normokalemic on active drug and those who became normokalemic on placebo. The former will be randomized in a 1:1 ratio between the same dose of ZS they received during the acute phase but only administered once a day (qd) or placebo, qd. Subjects on placebo during the Acute Phase who are normokalemic in the morning of Study Day 3, will be randomized to receive either 1.25 or 2.5 g ZS, qd as Subacute Phase treatment.

Safety and tolerability will be assessed on an ongoing basis by an Independent Data Safety Monitoring Board (DSMB). Each active dose group will consist of 150 patients per treatment group including the placebo control group for a total of 750 patients; the 1:1:1:1:1 allocation helps to optimize the multiple active dose comparisons to the respective placebo controls for the Subacute Phase.

  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).
  • Ability to have repeated blood draws or effective venous catheterization.
  • Women of childbearing potential must be practicing a highly effective method of birth control.

Exclusion Criteria:

  • Pseudohyperkalemia signs and symptoms, such as excessive fist clinching hemolyzed blood specimen, severe leukocytosis or thrombocytosis.
  • Subjects treated with lactulose, xifaxan or other nonabsorbed antibiotics for hyperammonemia within the last 7 days.
  • Subjects treated with resins (such as Sevelamer acetate or Sodium polystyrene sulfonate [SPS; e.g. Kayexalate®]), calcium acetate, calcium carbonate, or lanthanum carbonate, within the last 7 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 Ketoacidosis/Acidemia.
  • 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 ZS
  • 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.
  • Insulin-dependent diabetes mellitus
  • Subjects on dialysis
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01737697

  Show 44 Study Locations
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: NCT01737697     History of Changes
Other Study ID Numbers: ZS-003
Study First Received: November 19, 2012
Last Updated: November 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hyperkalemia
Metabolic Diseases
Water-Electrolyte Imbalance

ClinicalTrials.gov processed this record on October 21, 2014