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

NCT01493024 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ZS-002
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Hyperkalemia; Chronic Kidney Disease; Kidney Dysfunction

Outcome Measures

Primary Outcomes (1)

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

  The rate of fall in S-K levels during the initial 48 hours of study drug treatment between the placebo treated subjects and the ZS treated subjects measured on a log scale

  24 and 48 hours post first study drug dose

Secondary Outcomes (16)

• Serum Potassium (S-K) at Individual Time Points.

  First 48 hours of study

• Time Specific S-K Levels to Normalization

  48 and 72 hours post first study drug dose

• Time Specific Decreases in S-K Levels of > = 0.5 mmol/L

  24 and 48 hours post first study drug dose

• Percentage of Participants With Normal S-K Levels at End of Study Day 2

  48 hours post first study drug dose

• Urine Sodium Excretion

  24 and 48 hours post first study drug dose

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo (silicified microcrystalline cellulose) randomized to mimic escalating doses of experimental drug administered three times daily (TID) with meals.

Drug: Placebo

Zirconium silicate (ZS)

EXPERIMENTAL

Randomized escalating doses (0.3g, 3g and 10g) of ZS (fractionated, protonated, microporous zirconium silicate, an oral sorbent) administered 3 times daily (tid) with meals.

Drug: Zirconium silicate (ZS)

Interventions

Zirconium silicate (ZS) DRUG

Randomized escalating doses (0.3g, 3g and 10g) of ZS (fractionated, protonated microporous Zirconium Silicate, an oral sorbent) administered 3 times daily (tid) with meals.

Also known as: ZS-9

Zirconium silicate (ZS)

Placebo DRUG

Randomized to mimic escalating doses of experimental drug administered 3 times daily (tid) with meals.

Also known as: silicified microcrystalline cellulose

Placebo

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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ZS Pharma, Inc.: lead

Study Sites (9)

Southwest Clinical Research Institute

Tempe, Arizona, 85284, United States

Location

West Coast Clinical Trials

Costa Mesa, California, 92626, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32132, United States

Location

Elite Research Institute, Inc.

Miami, Florida, 33169, United States

Location

Compass Research Phase 1, LLC

Orlando, Florida, 32806, United States

Location

Lakeview Medical Research

Summerfield, Florida, 34491, United States

Location

Johnson County Clin-Trials

Lenexa, Kansas, 66219, United States

Location

Southwest Houston Research, Ltd

Houston, Texas, 77099, United States

Location

Renal Associates, P.A.

San Antonio, Texas, 78215, United States

Location

Related Publications (1)

• 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

MeSH Terms

Conditions

Hyperkalemia; Renal Insufficiency, Chronic

Interventions

zircon

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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 2
• 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: December 12, 2011
• First Posted: December 15, 2011
• Study Start: November 30, 2011
• Primary Completion: May 31, 2012
• Study Completion: June 30, 2012
• Last Updated: June 29, 2018
• Results First Posted: June 29, 2018

Record last verified: 2018-05

Locations

US (9)