Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects

NCT04217590 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: D9485C00001
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 36

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.

Conditions

Hyperkalemia

Outcome Measures

Primary Outcomes (1)

• Percentage of Responders

  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 (LIDI) and did not receive rescue therapy. Subjects with no data during the evaluation period were classified as non-responders. 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.

Secondary Outcomes (5)

• Maximum Pre-dialysis S-K Values After SIDI and LIDI Below or Equal to 5.5 mmol/L During Evaluation Period

  Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.

• Pre-dialysis S-K After LIDI Between 3.5 and 5.5 mmol/L During the Evaluation Period

  Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.

• Instances of Pre-dialysis S-K After LIDI Between 4.0 and 5.0 mmol/L During the Evaluation Period

  Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.

• Expected Number of Normokalaemic (S-K 4.0-5.0 mmol/L) Instances

  Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.

• Instances of Potassium Gradient of < 3.0 mmol/L After LIDI During the Evaluation Period

  Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.

Study Arms (2)

Sodium Zirconium Cyclosilicate (SZC)

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Sodium Zirconium Cyclosilicate DRUG

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.

Also known as: SZC; Lokelma; ZS

Sodium Zirconium Cyclosilicate (SZC)

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
• Subject must be ≥ 18 years of age inclusive, at the time of signing the informed consent form.
• 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.
• Receiving haemodialysis (or hemodiafiltration) 3 times a week for treatment of end-stage renal disease (ESRD) for at least 3 months before randomization.
• 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).
• Prescribed dialysate K concentration ≤ 3 mmol/L during screening.
• 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.
• Subjects must be receiving dietary counselling appropriate for ESRD subjects treated with haemodialysis / haemodiafiltration as per local guidelines, which includes dietary potassium restriction.

You may not qualify if:

• 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.
• 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).
• Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization.
• Presence of cardiac arrhythmias or conduction defects that require immediate treatment.
• 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.
• 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.
• 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.
• Participation in another clinical study with an investigational product administered in the last 1 month before screening.
• Haemoglobin \< 9 g/dL on screening (as assessed on Visit 1).
• 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.
• Severe leukocytosis (\> 20 × 109/L) or thrombocytosis (≥ 450 × 109/L) during screening.
• Polycythaemia (Hb \> 14 g/dL) during screening.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• 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.
• Previous randomisation in the present study.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (36)

Research Site

Baotou, 014040, China

Location

Research Site

Baotou, 14010, China

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Research Site

Beijing, 100029, China

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Beijing, 100044, China

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Beijing, 100191, China

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Beijing, 102206, China

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Changchun, 130021, China

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Changchun, 130041, China

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Dongguan, 523009, China

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Hangzhou, 310014, China

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Hefei, 230001, China

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Hohhot, 010017, China

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Jinan, 250014, China

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Lanzhou, 730000, China

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Lanzhou, 730030, China

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Nanchang, 330006, China

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Nanjing, 210011, China

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Ningbo, 315000, China

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Ningbo, 315010, China

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Shanghai, 200065, China

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Shanghai, 200080, China

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Shanghai, 200090, China

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Shanghai, 200120, China

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Shanghai, 200127, China

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Shanghai, 200232, China

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Shanghai, 200233, China

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Shanghai, 200240, China

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Shanghai, 201199, China

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Shenzhen, 518035, China

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Shenzhen, 518053, China

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Tianjin, 300052, China

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Ürümqi, CN-830004, China

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Wenzhou, 325000, China

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Wenzhou, 325027, China

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Yangzhou, 225001, China

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Research Site

Yinchuan, 750004, China

Location

Related Publications (2)

• Ni Z, Lu R, Xu X, Bian X, Zhou Z, Yang J, Luo Q, Chen M, Chen C, Sun X, Yu L, He Q, Jiang H, Yuan W, Li Y, Zhou R, Wang J, Zhang X, Zuo L, Meng X, Chang Z, Zhao J, Wessman P, Xiang P; DIALIZE China Study Group. DIALIZE China: A Phase IIIb, Randomized, Placebo-Controlled Study to Reduce Predialysis Hyperkalemia With Sodium Zirconium Cyclosilicate in Chinese Patients. Clin Ther. 2023 Jul;45(7):633-642. doi: 10.1016/j.clinthera.2023.04.014. Epub 2023 Jun 27.

  PMID: 37385905 DERIVED

• 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

Related Links

• CSP Redacted
• Statistical Analysis Plan
• CSR Synopsis

MeSH Terms

Conditions

Hyperkalemia

Interventions

sodium zirconium cyclosilicate; Streptozocin

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astazeneca.com

1-877-240-9479

Study Officials

• Zhaohui Ni

  Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2020
• First Posted: January 3, 2020
• Study Start: November 16, 2020
• Primary Completion: January 3, 2022
• Study Completion: January 3, 2022
• Last Updated: March 28, 2023
• Results First Posted: March 28, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

CN (36)