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Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects (DIALIZE China)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04217590
Recruitment Status : Not yet recruiting
First Posted : January 3, 2020
Last Update Posted : August 20, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC), as well as the appropriateness of the dosing mechanism, in Chinese end-stage renal disease (ESRD) patients on chronic haemodialysis.

Condition or disease Intervention/treatment Phase
Hyperkalemia Drug: Sodium Zirconium Cyclosilicate Drug: Placebo Phase 3

Detailed Description:
This is a randomized, double-blind, placebo-controlled study to determine the safety and efficacy of SZC in ESRD subjects with hyperkalaemia and on stable haemodialysis. This study consists of a screening period, an 8-week randomized treatment period, and a follow-up period. Approximately 134 stable haemodialysis subjects with persistent pre-dialysis hyperkalaemia will be enrolled in the study across research sites in China.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 134 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3b, Multicentre, Prospective, Randomized, Double-Blind, Placebo-Controlled Study to Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects
Estimated Study Start Date : December 11, 2020
Estimated Primary Completion Date : October 13, 2021
Estimated Study Completion Date : October 13, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dialysis
Drug Information available for: Zirconium

Arm Intervention/treatment
Experimental: Sodium Zirconium Cyclosilicate (SZC)
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 SZC 5g depending on dose level assigned to a patient per non-dialysis days.
Drug: Sodium Zirconium Cyclosilicate
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 SZC 5g depending on dose level assigned to a patient per non-dialysis days.
Other Name: SZC; Lokelma; ZS

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.
Drug: 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.




Primary Outcome Measures :
  1. Proportion of subjects in the following categories during the evaluation period: • maintain a pre-dialysis serum K between 4.0-5.0 mmol/L on 3 out of 4 dialysis treatments following the long interdialytic interval • do not receive rescue therapy [ Time Frame: Last 4 weeks of the treatment period ]
    To evaluate the efficacy of SZC as compared to placebo in keeping the S-K concentration between 4.0 and 5.0 mmol/L in subjects on haemodialysis


Secondary Outcome Measures :
  1. Pre-dialysis S-K values after Short Inter-dialytic Interval (SIDI) and Long Inter-dialytic Interval (LIDI) during the evaluation period [ Time Frame: Last 4 weeks of the treatment period ]
    To evaluate the efficacy of SZC as compared to placebo in maintaining the pre-dialysis SK concentration below 5.5 mmol/L

  2. Pre-dialysis S-K values after LIDI during the evaluation period [ Time Frame: Last 4 weeks of the treatment period ]
    To evaluate the efficacy of SZC as compared to placebo in maintaining the pre-dialysis LIDI S-K concentration between 5.5 and 3.5 mmol/L

  3. Instances of pre-dialysis after LIDI S-K between 4.0 and 5.0 mmol/L during the evaluation period [ Time Frame: Last 4 weeks of the treatment period ]
    To evaluate the efficacy of SZC as compared to placebo with respect to number of predialysis LIDI visits with S-K concentration between 4.0 and 5.0 mmol/L

  4. Instances of potassium gradient of < 3.0 mmol/L after LIDI during the evaluation period [ Time Frame: Last 4 weeks of the treatment period ]
    To evaluate the efficacy of SZC as compared to placebo in reducing the potassium gradient to below 3.0 mmol/L



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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
  2. Subject must be ≥ 18 years of age inclusive, at the time of signing the informed consent form.
  3. Subjects must have haemodialysis access consisting of an arteriovenous fistula, AV graft, or tunnelled (permanent) catheter which is expected to remain in place for the entire duration of the study.
  4. Receiving haemodialysis (or hemodiafiltration) 3 times a week for treatment of end-stage renal disease (ESRD) for at least 3 months before randomization.
  5. Pre-dialysis S-K > 5.4 mmol/L after long inter-dialytic interval and > 5.0 mmol/L after at least 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 haemodialysis / haemodiafltration prescription during screening with prescription (time, dialyzer, blood flow [Qb], dialysate flow rate [Qd] and bicarbonate concentration) expected to remain unchanged during study.
  8. Subjects must be receiving dietary counselling appropriate for ESRD subjects treated with haemodialysis / haemodiafiltration as per local guidelines, which includes dietary potassium restriction.

Exclusion Criteria:

  1. 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.
  2. Pseudohyperkalaemia secondary to haemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable).
  3. Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization.
  4. Presence of cardiac arrhythmias or conduction defects that require immediate treatment.
  5. Any medical condition, including active, clinically significant infection or liver disease, that in the opinion of the investigator or Sponsor may pose a safety risk to a subject in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation.
  6. History of QT prolongation associated with other medications that required discontinuation of that medication; congenital long QT syndrome or QTc(f) > 550 msec; uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication or with transient atrial fibrillation associated with dialysis or peridialytic period are permitted.
  7. Subjects treated with sodium polystyrene sulfonate (e.g. 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.
  8. Participation in another clinical study with an investigational product administered in the last 1 month before screening.
  9. Haemoglobin < 9 g/dL on screening (as assessed on Visit 1).
  10. Laboratory diagnosis of hypokalaemia (K < 3.5 mmol/L), hypocalcemia (Ca < 8.2 mg/d or albumin-corrected Ca < 8.0 mg/dL if the latter is used in local practice), hypomagnesemia (Mg < 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4 weeks preceding randomization.
  11. Severe leukocytosis (> 20 × 109/L) or thrombocytosis (≥ 450 × 109/L) during screening.
  12. Polycythaemia (Hb > 14 g/dL) during screening.
  13. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  14. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
  15. Previous randomisation in the present study.
  16. For women only - currently pregnant (confirmed with positive pregnancy test or uterine ultrasound if pregnancy test is questionable) or breast-feeding.
  17. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.
  18. Lack of compliance with haemodialysis prescription (both number and duration of treatments) during the two-week period preceding screening (100% compliance required).
  19. Subjects unable to take investigational product drug mix.
  20. Scheduled date for living donor kidney transplant.
  21. Subjects with a life expectancy of less than 6 months.
  22. Known hypersensitivity or previous anaphylaxis to SZC or to components thereof.
  23. History of alcohol or drug abuse within 2 years prior to randomization.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04217590


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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China
Research Site
Beijing, China, 102206
Research Site
Lanzhou, China, 730030
Research Site
Shanghai, China, 200127
Research Site
Shanghai, China, 200240
Research Site
Shenzhen, China, 518035
Research Site
Shenzhen, China, 518053
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Zhaohui Ni Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04217590    
Other Study ID Numbers: D9485C00001
First Posted: January 3, 2020    Key Record Dates
Last Update Posted: August 20, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Hyperkalemia
Water-Electrolyte Imbalance
Metabolic Diseases