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HyperkalemiaPhase 2NCT01493024

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

A Phase 2 study testing Zirconium silicate (ZS) in people with Hyperkalemia and Chronic Kidney Disease, run by ZS Pharma, Inc. at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Zirconium silicate (ZS)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
90 participants
Where
9 sitesUnited States
Study dates
30 Nov 2011to 30 Jun 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 14Show fewer
  • 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.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • West Coast Clinical Trials

    Costa Mesa, California, 92626

  • Riverside Clinical Research

    Edgewater, Florida, 32132

  • Southwest Houston Research, Ltd

    Houston, Texas, 77099

  • Johnson County Clin-Trials

    Lenexa, Kansas, 66219

  • Elite Research Institute, Inc.

    Miami, Florida, 33169

  • Compass Research Phase 1, LLC

    Orlando, Florida, 32806

  • Renal Associates, P.A.

    San Antonio, Texas, 78215

  • Lakeview Medical Research

    Summerfield, Florida, 34491

  • Southwest Clinical Research Institute

    Tempe, Arizona, 85284

Other trials in United States

About this study

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

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.

Read the 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, in a double-blind dose-escalating fashion (three separate cohorts), they will be randomized to receive one of the 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.

Being tested
Zirconium silicate (ZS), Placebo
Medical subject headings
Hyperkalemia, Renal Insufficiency, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Zirconium silicate (ZS)Drug

    Also called ZS-9

    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.

  • PlaceboDrug

    Also called silicified microcrystalline cellulose

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

Study groups in NCT01493024
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo (silicified microcrystalline cellulose) randomized to mimic escalating doses of experimental drug administered three times daily (TID) with meals.
Receives: Drug: Placebo
Zirconium silicate (ZS)ExperimentalRandomized escalating doses (0.3g, 3g and 10g) of ZS (fractionated, protonated, microporous zirconium silicate, an oral sorbent) administered 3 times daily (tid) with meals.
Receives: Drug: Zirconium silicate (ZS)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 24 and 48 hours post first study drug dose

Secondary outcomes (16)

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

    Serum potassium (S-K) at individual time points through Study day 3/0hour.

    Measured: First 48 hours of study

  2. Time Specific S-K Levels to Normalization

    Percent of subjects achieving S-K normalization (<=as defined by S-K levels of 3.5 to 4.9 mmol/L) from baseline at Study Days 2 and 3 at 0 hr.

    Measured: 48 and 72 hours post first study drug dose

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

    Percentage of participants achieving a 0.5mmol/L drop from baseline at Study Days 2 and 3 at 0 hr.

    Measured: 24 and 48 hours post first study drug dose

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

    Percentage (%) of subjects who achieve S-K normalization at end of Study Day 2

    Measured: 48 hours post first study drug dose

  5. Urine Sodium Excretion

    Urine sodium excretion compared between the combined placebo-treated controls and the ZS-treated subjects (measured throughout two 24-hour periods on Study Days 1 and 2).

    Measured: 24 and 48 hours post first study drug dose

  6. Urine Potassium Excretion

    Urine potassium excretion compared between the combined placebo-treated controls and the ZS-treated subjects (measured throughout two 24-hour periods on Study Days 1 and 2).

    Measured: 24 and 48 hours post study drug dose

  7. Urea Nitrogen Excretion

    Urea nitrogen excretion compared between the combined placebo-treated controls and the ZS-treated subjects (measured throughout two 24-hour periods on Study Days 1 and 2).

    Measured: 24 and 48 hours post study drug dose

  8. Blood Urea Nitrogen

    Blood urea nitrogen compared between the combined placebo-treated controls and the ZS-treated subjects (measured 24 \& 48 hours post dose on Study Days 2 and 3).

    Measured: 24 and 48 hours post study drug dose

  9. Serum Magnesium (S-Mg) Levels

    Serum magnesium compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 \& 48 hours post dose on Study Days 2 and 3).

    Measured: 24 and 48 hours post study drug dose

  10. Serum Calcium (S-Ca) Levels

    Serum calcium compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 \& 48 hours post dose on Study Days 2 and 3).

    Measured: 24 and 48 hours post study drug dose

  11. Serum Sodium (S-Na) Levels

    Serum sodium compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 \& 48 hours post dose on Study Days 2 and 3).

    Measured: 24 and 48 hours post study drug dose

  12. Serum Bicarbonate (HCO3) Levels

    Serum bicarbonate compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 \& 48 hours post dose on Study Days 2 and 3).

    Measured: 24 and 48 hours post study drug dose

  13. 24-hour Urinary Excretion of Potassium

    24-hour urinary excretion of potassium on Study Days 1 and Day 2

    Measured: 24 and 48 hours post study drug dose

  14. 24-hour Urinary Excretion of Sodium

    24-hour urinary excretion of sodium on Study Days 1 and Day 2

    Measured: 48 hours

  15. 24-hour Urinary Excretion of Urea Nitrogen

    24-hour urinary excretion of urea nitrogen on Study Days 1 and Day 2

    Measured: 48 hours

  16. 24-hour Urinary Excretion of Creatinine

    24-hour urinary excretion of creatinine on Study Days 1 and Day 2

    Measured: 48 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Dec 2011 (estimated)
  2. Study start30 Nov 2011
  3. Primary completion31 May 2012
  4. Study completion30 Jun 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01493024
Sponsor's protocol ID
ZS-002
Status last verified
May 2018
First submitted
12 Dec 2011
Last updated
29 Jun 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 32588430

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zirconium silicate (ZS) in people with Hyperkalemia and Chronic Kidney Disease, run by ZS Pharma, Inc. at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment (time frame: 24 and 48 hours post first study drug dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01493024, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2018.

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