Phase 2
N=90
Safety & Efficacy of Zirconium Silicate in Chronic Kidney Disease or Moderate Kidney Dysfunction With Mild Hyperkalemia
Hyperkalemia · Chronic Kidney Disease · Kidney Dysfunction
Bottom Line
View on ClinicalTrials.gov: NCT01493024 ↗Enrolled (actual)
90
Serious AEs
0.0%
Results posted
Jun 2018
Primary outcome: Primary: Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment — 0; -0.00035; -0.00169; -0.000143 log(mmol/L/hour)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Zirconium silicate (ZS) (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- ZS Pharma, Inc.
- Primary completion
- May 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment |
0; -0.00035; -0.00169; -0.000143; 0; -0.00045 | — |
| SECONDARY Serum Potassium (S-K) at Individual Time Points. |
5.14; 5.22; 5.02; 5.05; 4.97; 5.06 | — |
| SECONDARY Time Specific S-K Levels to Normalization |
90; 75; 95.8; 100; 90; 100 | — |
| SECONDARY Time Specific Decreases in S-K Levels of > = 0.5 mmol/L |
16.7; 33.3; 37.5; 33.3; 26.7; 41.7 | — |
| SECONDARY Percentage of Participants With Normal S-K Levels at End of Study Day 2 |
90; 75; 95.8; 100 | — |
| SECONDARY Urine Sodium Excretion |
91.5; 73.5; 81.7; 74.5; 74.4; 66.7 | — |
| SECONDARY Urine Potassium Excretion |
36.6; 32.2; 38.3; 30.3; 28.7; 32.0 | — |
| SECONDARY Urea Nitrogen Excretion |
525.0; 430.2; 481.0; 424.7; 389.2; 401.8 | — |
| SECONDARY Blood Urea Nitrogen |
24.50; 23.52; 25.16; 30.37; 24.05; 23.63 | — |
| SECONDARY Serum Magnesium (S-Mg) Levels |
1.93; 1.95; 1.93; 1.85; 1.92; 1.93 | — |
| SECONDARY Serum Calcium (S-Ca) Levels |
9.46; 9.37; 9.48; 9.50; 9.39; 9.36 | — |
| SECONDARY Serum Sodium (S-Na) Levels |
139.4; 139.1; 140.0; 137.7; 140.1; 138.8 | — |
| SECONDARY Serum Bicarbonate (HCO3) Levels |
28.1; 28.6; 28.1; 27.4; 28.6; 29.2 | — |
| SECONDARY 24-hour Urinary Excretion of Potassium |
56.5; 62.4; 58.9; 46.9; 64.7; 89.4 | — |
| SECONDARY 24-hour Urinary Excretion of Sodium |
145; 132.8; 124.0; 114.8; 169.4; 173.7 | — |
| SECONDARY 24-hour Urinary Excretion of Urea Nitrogen |
7.66; 7.59; 7.03; 6.74; 8.30; 8.51 | — |
| SECONDARY 24-hour Urinary Excretion of Creatinine |
1175.39; 1149.00; 1126.26; 1015.67; 1157.12; 1027.50 | — |
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.
Eligibility 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.
Data sourced from ClinicalTrials.gov (NCT01493024). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.