E875 Hyperkalaemia Hyperkalaemia
Conditions
Interventions
Sodium Zirconium Cyclosilicate (SZC)
Powder for oral suspension in a sachet 5 g or 10 g SZC Oral
Single dose contains 5 to 15 g SZC that should be suspended in 45 mL of water by participant and admini
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Informed Consent 1 Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol 2 Provision of signed and dated, written ICF prior to any mandatory study-specific procedures, sampling, and analyses (Appendix A) Age 3 Must be = 18 years of age, at the time of signing the ICF. For participants < 20 years of age and enrolled in Japan, a written informed consent should be obtained from the participant and his or her legally acceptable representative. Type of Participant and Disease Characteristics 4 Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of ESRD for = 4 months before enrollment 5 Must have hemodialysis access consisting of an arteriovenous fistula, arteriovenous graft, or tunneled (permanent) catheter which is expected to remain in place for the entire duration of the study 6 At least 2 out of 3 pre-dialysis S K values = 5.5 mmol/L after the LIDI during screening Contraception and Reproduction Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 7 Negative pregnancy test for female participants of childbearing potential 8 Female participants must be 1 year postmenopausal, surgically sterile, or using one highly effective form of birth control (defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly). They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study and willing to remain on the birth control until 12 weeks after the last dose. See Section 5.3.4.
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1 Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not considered a screening failure: sampling or full screening can be postponed to a later time as applicable) 2 Presence of cardiac arrhythmias or conduction defects that require immediate treatment 3 Participants who have a pacemaker or implantable cardiac defibrillator 4 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 participant in this study, confound safety or efficacy assessment and jeopardize the quality of the data, or interfere with study participation, or any other restrictions or contraindications in the local prescribing information for SZC 5 History of QT prolongation associated with other medications that required discontinuation of that medication 6 Congenital long QT syndrome 7 QTcF > 550 msec 8 Symptomatic or uncontrolled AF despite treatment, or asymptomatic sustained ventricular tachycardia Prior/Concomitant Therapy 9 Treated with SPS (eg, Kayexalate, Resonium), CPS (Resonium Calcium), patiromer (Veltassa), or SZC (Lokelma) within 7 days before screening Prior/Concurrent Clinical Study Experience 10 Participation in another clinical study with an investigational product administered within one month before screening Other Exclusions 11 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 12 Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements 13 Previous randomization in the present study 14 Females who are pregnant (confirmed with positive pregnancy test or a uterine ultrasound if pregnancy test result is questionable), breastfeeding, or planning to become pregnant during the study 15 Known hypersensitivity or previous anaphylaxis to SZC or to components thereof 16 Scheduled date for living donor kidney transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| •measurement of Time to first occurrence of SCD, stroke, or hospitalization/intervention/ED visit due to arrhythmias (atrial fibrillation [AF], bradycardia, asystole, ventricular tachyarrhythmias [VT]) NAME OF THE RESULT: •To evaluate the efficacy of SZC compared with placebo in reducing the incidence of the primary composite endpoint of SCD, all stroke, or hospitalization/intervention/emergency department (ED) visit due to arrhythmias PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: At time of the first ocurrence | — |
Secondary
| Measure | Time frame |
|---|---|
| • measurement of S K > 6.5 mmol/L (yes/no) after the LIDI NAME OF THE RESULT: • To evaluate the efficacy of SZC compared with placebo in preventing severe hyperkalemia at one year PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: At the 12 month visit ;• Identification of Time to SCD NAME OF THE RESULT: • To evaluate the efficacy of SZC compared with placebo in reducing the incidence of SCD PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: During the study ;• Identification of Time to CV death NAME OF THE RESULT: • To evaluate the efficacy of SZC compared with placebo in reducing the incidence of CV death PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time to CV death ;• Identification of Time to death of any cause NAME OF THE RESULT: • To evaluate the efficacy of SZC compared with placebo in reducing the incidence of all cause mortality PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time to death of any cause ;• Time valuation to first instance of rescue therapy use for hyperkalemia NAME OF THE RESULT: • To evaluate the efficacy of SZC compared with placebo in reducing the need for rescue therapy for hyperkalemia PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time to first instance ;• measurement of Time to first occurrence of SCD, stroke, or hospitalization/intervention/ED | — |
Countries
Argentina, Austria, Brazil, Bulgaria, Canada, China, Czech Republic, Germany, Hungary, Italy, Japan, Mexico, Peru, Poland, Russian Federation, Slovakia, Spain, Taiwan, Ukraine, United Kindgdom
Contacts
Public ContactMARIA DEL CARMEN MOYA
ASTRAZENECA PERU S.A.
Outcome results
None listed