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

Launched by ASTRAZENECA · Jan 2, 2020

Keywords

ClinConnect Summary

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.

Gender

ALL

Eligibility 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.