Safety & Efficacy of Zirconium Silicate in Chronic Kidney Disease or Moderate Kidney Dysfunction With Mild Hyperkalemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ZS Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01493024
First received: December 12, 2011
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

It is hypothesized that zirconium silicate is safe and well tolerated and more effective than placebo (alternative hypothesis) in lowering serum potassium levels in subjects with serum potassium between 5 - 6.0 mmol/l versus no difference between zirconium silicate and placebo (null hypothesis). It is hypothesized that zirconium silicate even up to the top dose of 10g three times a day is well tolerated.


Condition Intervention Phase
Hyperkalemia
Chronic Kidney Disease
Kidney Dysfunction
Drug: Zirconium silicate (ZS)
Drug: silicified microcrystalline cellulose
Phase 2

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, Prospective, Randomized, Placebo-Controlled, Double-blind Dose Escalating Study of Safety, Tolerability and Pharmacodynamics of Zirconium Silicate in Chronic Kidney Disease and Moderate Kidney Dysfunction With Mild 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: during the first 48 hours ] [ Designated as safety issue: Yes ]
    To evaluate the effect on serum potassium (S-K)) of 3 different doses of zirconium silicate (ZS) administered 3 times daily for 48 hours (with up to an additional 48 hours of three times a day dosing for subjects whose S-K has not normalized [3.5 - 4.9 mmol/l] after the initial 48 hours) to subjects with moderate Chronic Kidney Disease (CKD as defined by a glomerular filtration rate (GFR) between 40-60ml/min) and mild hyperkalemia (S-K between 5-6.0 mmol/l).


Secondary Outcome Measures:
  • Identify optimal zirconium silicate dose to normalize serum potassium levels between 3.5 - 4.9 mmol/L without causing serious adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 90
Study Start Date: November 2011
Study Completion Date: June 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zirconium silicate (ZS)
Randomized escalating doses (0.3g, 3g and 10g) of ZS (fractionated, protonated, microporous zirconium silicate, an oral sorbent) administered 3 times (tid) daily with meals.
Drug: Zirconium silicate (ZS)
Randomized escalating doses (0.3g, 3g and 10g) of ZS (fractionated, protonated microporous Zirconium Silicate, an oral sorbent), or placebo, administered 3 times (tid) daily with meals.
Other Name: ZS-9
Placebo Comparator: silicified microcrystalline cellulose
Randomized to mimic escalating doses of experimental drug administered 3 times (tid) daily with meals.
Drug: silicified microcrystalline cellulose
Randomized to mimic escalating doses of experimental drug administered 3 times (tid) daily with meals.
Other Name: PROSOLV SMCC 90

Detailed Description:

A total of 90 subjects with moderate CKD (defined as GFR between 40- 60ml/min) and mild hyperkalemia (S-K between 5-6 mmol/l) will be enrolled in the study where they, in a double-blind dose-escalating fashion (three separate cohorts), will be randomized to receive escalating doses of ZS (0.3g, 3g and 10g) or placebo, administered 3 times (tid) daily with meals. The first cohort will have 18 subjects while both of the second and third cohorts will have 36 subjects for a total of 90 subjects.

Safety and tolerability will be assessed by an Independent Data Safety Monitoring Board (DSMB) after completion of each cohort, before escalation to the next dose level will be allowed. The next dose escalation will happen no sooner than one week after the last dose of study drug at the previous dosing level has been administered. Safety stopping rules will be specified for this study. Within the first dose level (300 mg dose), 12 subjects will be randomized to receive ZS, whereas 6 subjects will be randomized to receive placebo for a total of 18 subjects in this first cohort. In the next two cohorts (3 g and 10 g doses), 24 subjects per cohort will be randomized to receive ZS, whereas 12 subjects per cohort will be randomized to receive placebo for a total of 36 subjects in each of the second and third cohorts.

  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.
  • GFR between 40-60 ml/min as estimated by the CKD-EPI equation. After screening two additional GFR values of between 40-60ml/min must be repeated within 24 hours before inclusion is allowed.
  • S-K between 5.0 - 6.0 mmol/l (inclusive) during Study Day 0.
  • Ability to have repeated blood draws or effective venous catheterization.
  • Women of child bearing potential must be practicing a highly effective method of birth control.

Exclusion Criteria:

  • Pseudohyperkalemia such as excessive fist clinching 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 or calcium carbonate, lanthanum carbonate, Sodium polystyrene sulfonate (SPS; e.g. Kayexalate®) 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.
  • Cancer within the last 5 years (other than successfully treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or early stage prostate cancer).
  • 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 Zirconium Silicate or to components thereof.
  • Subjects who have cardiac arrhythmias that require immediate treatment.
  • Subjects with ECG changes associated with hyperkalemia.
  • Subjects with acute kidney injury.
  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: NCT01493024

Locations
United States, Arizona
Southwest Clinical Research Institute
Tempe, Arizona, United States, 85284
United States, California
West Coast Clinical Trials
Costa Mesa, California, United States, 92626
United States, Florida
Riverside Clinical Research
Edgewater, Florida, United States, 32132
Elite Research Institute, Inc.
Miami, Florida, United States, 33169
Compass Research Phase 1, LLC
Orlando, Florida, United States, 32806
Lakeview Medical Research
Summerfield, Florida, United States, 34491
United States, Kansas
Johnson County Clin-Trials
Lenexa, Kansas, United States, 66219
United States, Texas
Southwest Houston Research, Ltd
Houston, Texas, United States, 77099
Renal Associates, P.A.
San Antonio, Texas, United States, 78215
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: NCT01493024     History of Changes
Other Study ID Numbers: ZS-002
Study First Received: December 12, 2011
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hyperkalemia
Kidney Diseases
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Water-Electrolyte Imbalance
Metabolic Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on July 22, 2014