Safety & Efficacy of Zirconium Silicate in Mild to Moderate Hyperkalemia

NCT01737697 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ZS-003
• Study Type: interventional
• Target: 754
• Locations: 2 countries
• Sites: 44

Brief Summary

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).

Conditions

Hyperkalemia

Outcome Measures

Primary Outcomes (2)

• Exponential Rate of Change in Serum Potassium (S-K) Levels During the Initial 48 Hours of Study Drug Treatment.

  Through 48 hours acute phase

• Exponential Rate of Change in S-K Levels in the Subacute Phase.

  Through 12 days subacute phase (Day 3 through Day 15)

Secondary Outcomes (7)

• Percentage of Subjects Who Achieve Normalization in S-K Levels After 48 Hours of Treatment

  Through 48 hours acute phase

• Mean Change From Baseline in S-K at All Time Points Acute Phase

  Through 48 hours acute phase. In particular, at Baseline; 1, 2, 4 hour Post 1st Dose on Study Day 1; 0 hour Pre-dose, 1, 4 hour Post 1st Dose on Study Day 2; and 0 hour Pre-dose on Study Day 3.

• Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase

  Through 48 hours acute phase. In particular, 1, 2, 4 hour Post 1st Dose on Study Day 1; 0 hour Pre-dose, 1, 4 hour Post 1st Dose on Study Day 2; and 0 hour Pre-dose on Study Day 3.

• Time Subjects Remain Normokalemic (Subacute Phase)

  Through 18 days (12 days treatment, 6 days follow-up) of subacute phase

• Percentage of Subjects Within Each Treatment Group Who Retained Normal S-K Values at End of Subacute Phase

  Through 18 days of subacute phase (12 days treatment, 6 days follow-up)

Study Arms (4)

Zirconium silicate (acute phase)

EXPERIMENTAL

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)

Placebo (acute phase)

PLACEBO COMPARATOR

Placebo ( silicified microcrystalline cellulose) randomized to mimic doses of experimental drug administered 3 times (tid) daily with meals.

Drug: Placebo (acute phase)

Zirconium silicate (subacute phase)

EXPERIMENTAL

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)

Placebo (subacute phase)

PLACEBO COMPARATOR

Placebo (silicified microcrystalline cellulose) randomized to mimic doses of experimental drug administered once a day (qd) prior to the morning meal for 12 days.

Drug: Placebo ( subacute phase)

Interventions

Zirconium silicate (acute phase) DRUG

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.

Also known as: ZS

Zirconium silicate (acute phase)

Zirconium silicate (subacute phase) DRUG

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.

Also known as: ZS

Zirconium silicate (subacute phase)

Placebo (acute phase) DRUG

Randomized to mimic doses of experimental drug administered 3 times (tid) daily with meals for 48 hours during the acute phase.

Also known as: Silicified microcrystalline cellulose

Placebo (acute phase)

Placebo ( subacute phase) DRUG

Randomized to mimic doses of experimental drug administered once a day prior to the morning meal for 12 days during the subacute phase.

Also known as: Silicified microcrystalline cellulose

Placebo (subacute phase)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• ZS Pharma, Inc.: lead

Study Sites (44)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

Saadat Ansari Internal Medicine

Huntsville, Alabama, 35801, United States

Location

Aspire Clinical Studies, LLC

Glendale, Arizona, 85301, United States

Location

Southwest Clinical Research Institute

Tempe, Arizona, 85284, United States

Location

California Institute of Renal Research

Chula Vista, California, 91910, United States

Location

Torrance Clinical Research

Lomita, California, 90717, United States

Location

Academic Medical Research Institute

Los Angeles, California, 90022, United States

Location

Mohammad Ismail, Inc

Paramount, California, 90723, United States

Location

Apex Research of Riverside

Riverside, California, 92505, United States

Location

Capital Nephrology Clinical Group

Sacramento, California, 95825, United States

Location

Pikes Peak Nephrology Associates

Colorado Springs, Colorado, 80909, United States

Location

Denver Nephrologists, PC

Denver, Colorado, 80230, United States

Location

Nephrology and Hypertension Associates

Middlebury, Connecticut, 06762, United States

Location

JEM Research Institute

Atlantis, Florida, 33462, United States

Location

Clinical Research of Brandon

Brandon, Florida, 33511, United States

Location

Meridien Research

Brooksville, Florida, 34601, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32123, United States

Location

Endocrinology of Central Florida

Lake Mary, Florida, 32746, United States

Location

Meridien Research

Lakeland, Florida, 33805, United States

Location

San Marcus Research Clinic

Miami, Florida, 33015, United States

Location

Medical Consulting Center

Miami, Florida, 33125, United States

Location

Elite Research Institute

Miami, Florida, 33169, United States

Location

Prevention & Strengthening Solutions, Inc

Miramar, Florida, 33023, United States

Location

PCCC of Volusia

New Smyrna Beach, Florida, 32168, United States

Location

Meridien Research

St. Petersburg, Florida, 33709, United States

Location

Lakeview Medical Research

Summerfield, Florida, 34491, United States

Location

Clinical Research Trials of Florida

Tampa, Florida, 33607, United States

Location

Metabolic Research Institute

West Palm Beach, Florida, 33401, United States

Location

Research by Design

Evergreen Park, Illinois, 60805, United States

Location

Professional Research Network of Kansas, LLC

Wichita, Kansas, 67213, United States

Location

Washington Nephrology Associates

Bethesda, Maryland, 20814, United States

Location

Nephrology Center DBA, Paragon Health PC

Kalamazoo, Michigan, 49007, United States

Location

The Center for Clinical Trials

Biloxi, Mississippi, 39531, United States

Location

Clinical Research Consultants, LLC

Kansas City, Missouri, 64111, United States

Location

United Medical Associates

Binghamton, New York, 13903, United States

Location

Life Medi-Research and Management

Brooklyn, New York, 11206, United States

Location

Doylestown Hospital Medical Research

Doylestown, Pennsylvania, 18901, United States

Location

South Carolina Nephrology & Hypertension

Orangeburg, South Carolina, 29118, United States

Location

Carolina Diabetes and Kidney Center

Sumter, South Carolina, 29150, United States

Location

Southwest Houston Research, Ltd

Houston, Texas, 77099, United States

Location

Clinical Advancement Center, PLLC

San Antonio, Texas, 78215, United States

Location

Southern Utah Kidney and Hypertension Center

St. George, Utah, 84770, United States

Location

Renal Research

Gosford, New South Wales, 02250, Australia

Location

Melbourne Renal Research Group

Reservoir, Victoria, 03073, Australia

Location

Related Publications (4)

• Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020 Jun 26;6(6):CD013165. doi: 10.1002/14651858.CD013165.pub2.

  PMID: 32588430 DERIVED

• Amin AN, Menoyo J, Singh B, Kim CS. Efficacy and safety of sodium zirconium cyclosilicate in patients with baseline serum potassium level >/= 5.5 mmol/L: pooled analysis from two phase 3 trials. BMC Nephrol. 2019 Dec 2;20(1):440. doi: 10.1186/s12882-019-1611-8.

  PMID: 31791288 DERIVED

• Friedman PA, Scott CG, Bailey K, Baumann NA, Albert D, Attia ZI, Ladewig DJ, Yasin O, Dillon JJ, Singh B. Errors of Classification With Potassium Blood Testing: The Variability and Repeatability of Critical Clinical Tests. Mayo Clin Proc. 2018 May;93(5):566-572. doi: 10.1016/j.mayocp.2018.03.013.

  PMID: 29728199 DERIVED

• Packham DK, Rasmussen HS, Lavin PT, El-Shahawy MA, Roger SD, Block G, Qunibi W, Pergola P, Singh B. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015 Jan 15;372(3):222-31. doi: 10.1056/NEJMoa1411487. Epub 2014 Nov 21.

  PMID: 25415807 DERIVED

MeSH Terms

Conditions

Hyperkalemia

Interventions

zircon

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: AstraZeneca Clinical Study Information Center
• Organization: ZS Pharma, Inc.

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Henrik Rasmussen, MD

  ZS Pharma, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: November 29, 2012
• Study Start: November 30, 2012
• Primary Completion: October 31, 2013
• Study Completion: November 30, 2013
• Last Updated: October 12, 2018
• Results First Posted: October 12, 2018

Record last verified: 2018-09

Locations

US (42); AU (2)