A Study to Test Whether ZS (Sodium Zirconium Cyclosilicate) Can Reduce the Incidence of Increased Blood Potassium Levels Among Dialized Patients. (DIALIZE)

February 10, 2020 updated by: AstraZeneca

A Phase 3b, Multicenter, Prospective, Randomized, Double Blind, Placebocontrolled Study to Reduce Incidence of Pre-dialysis Hyperkalemia With Sodium Zirconium Cyclosilicate (DIALIZE)

The purpose of this study is to evaluate the efficacy of ZS in the treatment of hyperkalemia in patients on hemodialysis.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

196

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Hamamatsu-shi, Japan, 432-8036
        • Research Site
      • Kumamoto-shi, Japan, 860-4112
        • Research Site
      • Miyagi-gun, Japan, 981-0112
        • Research Site
      • Nagano-shi, Japan, 388-8004
        • Research Site
      • Niigata-shi, Japan, 950-2087
        • Research Site
      • Ora-gun, Japan, 370-0615
        • Research Site
      • Osaka-shi, Japan, 543-0052
        • Research Site
      • Sakai-shi, Japan, 599-8272
        • Research Site
      • Sashima-gun, Japan, 306-0433
        • Research Site
      • Sendai-shi, Japan, 980-0801
        • Research Site
      • Shinjuku-ku, Japan, 169-0075
        • Research Site
      • Toride-shi, Japan, 302-0022
        • Research Site
      • Tsukuba-shi, Japan, 305-0861
        • Research Site
      • Wakayama-shi, Japan, 640-8335
        • Research Site
      • Yachiyo-shi, Japan, 276-0031
        • Research Site
      • Yokosuka-shi, Japan, 238-0004
        • Research Site
      • Kemerovo, Russian Federation, 650066
        • Research Site
      • Kolomna, Russian Federation
        • Research Site
      • Moscow, Russian Federation, 141007
        • Research Site
      • Novosibirsk, Russian Federation, 630087
        • Research Site
      • Omsk, Russian Federation, 644111
        • Research Site
      • Penza, Russian Federation, 440034
        • Research Site
      • Podolsk, Russian Federation
        • Research Site
      • Rostov-on-Don, Russian Federation, 344029
        • Research Site
      • Saint-Petersburg, Russian Federation, 198205
        • Research Site
      • Saint-Petersburg, Russian Federation, 191104
        • Research Site
      • St-Petersburg, Russian Federation, 196247
        • Research Site
      • Yaroslavl, Russian Federation, 150062
        • Research Site
      • Yekaterinburg, Russian Federation, 620102
        • Research Site
      • Cardiff, United Kingdom, CF14 4XW
        • Research Site
      • Hull, United Kingdom, HU3 2JZ
        • Research Site
      • Leicester, United Kingdom, LE5 4PW
        • Research Site
      • London, United Kingdom, EC1A 7BE
        • Research Site
      • London, United Kingdom, SE5 9RS
        • Research Site
      • London, United Kingdom, SW17 0QT
        • Research Site
      • London, United Kingdom, SM5 1AA
        • Research Site
      • Swansea, United Kingdom, SA6 6NL
        • Research Site
      • York, United Kingdom, YO31 8HE
        • Research Site
    • California
      • Los Angeles, California, United States, 90025
        • Research Site
      • Los Angeles, California, United States, 90022
        • Research Site
      • Ontario, California, United States, 91762
        • Research Site
      • San Dimas, California, United States, 91773
        • Research Site
      • Whittier, California, United States, 90606
        • Research Site
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Research Site
      • Saint Louis, Missouri, United States, 63110
        • Research Site
    • New Jersey
      • Paterson, New Jersey, United States, 07504
        • Research Site
    • New York
      • Bronx, New York, United States, 10461
        • Research Site
      • Fresh Meadows, New York, United States, 11365
        • Research Site
      • Great Neck, New York, United States, 11021
        • Research Site
      • Ridgewood, New York, United States, 11385
        • Research Site
    • Rhode Island
      • East Providence, Rhode Island, United States, 02914
        • Research Site
    • Texas
      • El Paso, Texas, United States, 79924
        • Research Site
      • Houston, Texas, United States, 77004
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Provision of informed consent prior to any study specific procedures
  2. Female or male aged ≥ 18 years at screening Visit 1. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
  3. Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of endstage renal disease (ESRD) for at least 3 months before randomization.
  4. Patients must have hemodialysis access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter which is expected to remain in place for the entire duration of the study.
  5. Pre-dialysis serum K >5.4 mmol/L after long inter-dialytic interval and >5.0 mmol/L after one short inter-dialytic interval during screening (as assessed by central lab).
  6. Prescribed dialysate K concentration ≤ 3 mmol/L during screening
  7. Sustained Qb ≥200 ml/min and spKt/V ≥1.2 (or URR ≥ 63) on stable hemodialysis/hemodiafltration prescription during screening with prescription (time, dialyzer, blood flow [Qb], dialysate flow rate [Qd] and bicarbonate concentration) expected to remain unchanged during study
  8. Heparin dose (if used) must be stable during screening and expected to be stable during the study
  9. Subjects must be receiving dietary counseling appropriate for ESRD patients treated with hemodialysis/hemodiafiltration as per local guidelines, which includes dietary potassium restriction.

Exclusion Criteria:

  1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca, including ZS Pharma staff and/or staff at the study site)
  2. Hemoglobin <9 g/dL on screening (as assessed on Visit 1)
  3. Lack of compliance with hemodialysis prescription (both number and duration of treatments) during the two-week period preceding screening (100% compliance required)
  4. Patients treated with sodium polystyrene sulfonate (SPS, Kayexalate, Resonium), calcium polystyrene sulfonate (CPS, Resonium calcium) or patiromer (Veltassa) within 7 days before screening or anticipated in requiring any of these agents during the study
  5. Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis) within 12 weeks prior to randomization
  6. Laboratory diagnosis of hypokalemia (K < 3.5 mmol/L), hypocalcemia (Ca < 8.2 mg/dL; for Japan hypocalcemia is defined as albumin-corrected Ca < 8.0 mg/dL), hypomagnesemia (Mg < 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4 weeks preceding randomization
  7. Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable).
  8. Severe leukocytosis (>20× 10^9/L) or thrombocytosis (≥450 × 10^9/L) during screening
  9. Polycythemia (Hb >14 g/dL) during screening
  10. Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization
  11. Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug
  12. Patients unable to take oral ZS drug mix
  13. Scheduled date for living donor kidney transplant
  14. Patients with a life expectancy of less than 6 months
  15. Female patients who are pregnant or breastfeeding
  16. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.
  17. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
  18. Participation in another clinical study with an investigational product during the last 1 month before screening
  19. Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation
  20. Presence of cardiac arrhythmias or conduction defects that require immediate treatment
  21. History of alcohol or drug abuse within 2 years prior to randomization
  22. Previous randomization in the present study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.

Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) .

Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.

Experimental: Sodium Zirconium Cyclosilicate (ZS)
Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days.

Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) .

Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Responders
Time Frame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.
A subject was considered to be a responder if, during the evaluation period, they maintained a pre-dialysis serum potassium (S-K) between 4.0 and 5.0 mmol/L on at least 3 out of 4 dialysis treatments following the long inter-dialytic interval and did not receive rescue therapy. The S-K levels used for this analysis were based on the measurements obtained by the central laboratory.
Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.
Percentage of Responders When Accounting for Missing Central Laboratory Serum Potassium Data
Time Frame: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.
The sensitivity analysis assessed the impact of subjects classified as non-responders due to missing serum potassium (S-K) data. Missing central lab (c-lab) pre-dialysis values were imputed using corresponding pre-dialysis i-STAT (a portable blood analyser) measurements. In addition, a "last observation carried forward" (LOCF) approach was utilized to further impute missing values of pre-dialysis S-K during the evaluation period. This technique will replace missing c-lab S-K values with the last available non-missing pre-dialysis LIDI observation recorded for that patient (and this could be a c-lab value or an imputed c-lab value). The Primary endpoint analysis was repeated on the imputed data.
Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients Needing Rescue Therapy
Time Frame: An 8 week overall treatment period (a 4 week adjustment phase plus a 4 week evaluation phase) and a 2 week follow up period.
Patients requiring any urgent intervention consistent with local practice patterns to reduce serum potassium (S-K) including insulin/glucose, beta-adrenergic agonists, sodium bicarbonate, K binders or any form of renal replacement therapy.
An 8 week overall treatment period (a 4 week adjustment phase plus a 4 week evaluation phase) and a 2 week follow up period.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Steven Fishbane, MD, NSUH,Dept of Medicine,300 Community Drive,Manhasset,NY11030

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 14, 2017

Primary Completion (Actual)

November 7, 2018

Study Completion (Actual)

November 7, 2018

Study Registration Dates

First Submitted

September 26, 2017

First Submitted That Met QC Criteria

October 2, 2017

First Posted (Actual)

October 6, 2017

Study Record Updates

Last Update Posted (Actual)

February 20, 2020

Last Update Submitted That Met QC Criteria

February 10, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • D9480C00006
  • 2017-003029-14 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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