Hyperkalaemia MedDRA version: 21.1 Level: LLT Classification code 10020647 Term: Hyperkalemia System Organ Class: 100000004861
Conditions
Interventions
Product Name: Sodium zirconium cyclosilicate
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: Not assigned
CAS Number: 242800-27-7
Other descriptive name: SODIUM ZIRCONIUM CYCLOSIL
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of written informed consent of the participant or legal representative, and informed assent from the participant (as appropriate) 2. Female or male from birth to 5.0 mmol/L at Screening. Two consecutive i STAT K+ values, measured 60 (±15) minutes apart, both >5.0 mmol/L and measured within 1 day before the first dose of SZC on CP Study Day 1. (b)For participants 6.0 mmol/L at Screening, measured within 1 day before the first dose of SZC on CP Study Day 1. Note that if Day 1 is the same as the Screening day, the 60 (±15) minute K+ value is the same as the Day 1 time 0 K+ value. However, if Day 1 is not the same day as Screening, then the participant will actually have 3 i STAT-K+ values measured before starting treatment in the CP and the third value which is taken on Day 1 time 0 must also be hyperkalaemic. 5. Using digital ECG, QT interval corrected by Bazett's method (QTcB) must meet the age-appropriate parameters at Screening: (a)For participants aged 0 to =3 days after birth: 3 days to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Neonates with a gestational age <37 weeks at birth or a birth weight <2500 g. 2. Term and preterm neonates with suspected conditions predisposing them to intestinal ischemia (eg, perinatal hypoxia or sepsis). 3. Participants with pseudohyperkalaemia caused by excessive fist clenching to enable venepuncture, by haemolysed blood specimens, or by severe leukocytosis or thrombocytosis. 4. Participants with hyperkalaemia due to soft-tissue damage from crush injury or burns. 5. Participants with hyperkalaemia due to a secondary cause, such as dehydration, excessive use of K+ supplements, or drug use (eg, betaadrenergic antagonists) and that would be more appropriately treated with other interventions (eg, fluid resuscitation, dose adjustments of medications) 6. Participants treated with lactulose, rifaximin (XIFAXAN™), or other nonabsorbed antibiotics for hyperammonaemia within the last 7 days. 7. Participants treated with CPS, sodium polystyrene sulfonate (eg, KAYEXALATE™), or patiromer within the last 4 days. 8. Participants with a life expectancy of less than 3 months. 9. Participants who are known to have tested Human Immunodeficiency Virus (HIV) positive. 10. Presence of any condition which, in the opinion of the Investigator, places the participant at undue risk or potentially jeopardises the quality of the data to be generated. 11. Known hypersensitivity or previous anaphylaxis to SZC or to components thereof. 12. Participants with cardiac arrhythmias that require immediate treatment. 13. Participants with a family history of long QT syndrome. 14. Participants on haemodialysis. 15. Participants with a history of bowel obstruction. 16. Participants with severe gastrointestinal disorder or major gastrointestinal surgery (eg, large bowel resection). 17. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 18. Previous treatment with SZC. 19. Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry. 20. Previous enrolment in the present study. 21. Females who are pregnant, breastfeeding, or planning to become pregnant. 22. 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. 23. For the LTMP only: participants who are normokalaemic at Visit 8b and are receiving placebo at Visit 8a of the MP unless they received rescue treatment. 24. If the participant has evidence of Coronavirus disease 2019 (COVID-19) within 2 weeks prior to enrolment (a positive COVID-19 test or suspicion of COVID-19 infection) the participant cannot be enrolled in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 28-day maintenance phase (MP) primary objective: To compare the effect of SZC vs placebo on maintaining normokalaemia during the MP Correction phase (CP) primary objective: To evaluate SZC efficacy of different dose levels (DLs) on achieving normokalaemia during the CP;Secondary Objective: CP secondary objectives evaluate SZC DLs on the following achieving normokalaemia within the first 72 hrs time to achieving normokalaemia during the CP the reduction of S-K+ levels during the CP time to reduction of S-K+ levels during the CP MP secondary objectives evaluate SZC vs placebo on the following: time from randomisation to relapse of hyperkalaemia; the proportion of participants with normokalaemia per visit over the MP the change in S-K+ levels over the MP time to increase in S-K+ during the MP proportion of days of normokalaemia during the MP; mean S-K+ during the MP proportion of participants experiencing hypo- or hyperkalaemia during the MP serum aldosterone (S-Aldo) at the end of the MP plasma electrolytes(including bicarbonate)and spot urinary pH and electrolytes Long term maintenance phase(LTMP)objectives: To evaluate long term maintenance of normokalaemia during treatment with SZC Acceptability and palatability of SZC is evaluated in all study phases;Primary end point(s): 28-day MP primary endpoint (primary analysis endpoint): The proportion of participants in whom normokalaemia can be maintained throughout the MP Correction phase primary endpoint: The proportion of participants in whom serum K+ (S-K+) decreases by =0.5 mmol/L and who achieve normokalaemia at (by or before) 24, 48 and 72 hours during CP.;Timepoint(s) of evaluation of this end point: Correction Phase 24, 48 and 72 hours Maintenance Phase 28 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: CP secondary endpoints: - 0, 24, 48, 72 hours - 0, 24, 48, 72 hours - 0, 24, 48, 72 hours - 0, 24, 48, 72 hours - Day 1 and 3 MP secondary endpoints: - Days 1, 7, 14, 21, 28 - Days 1, 7, 14, 21, 28 - Days 1, 7, 14, 21, 28 - Days 1, 7, 14, 21, 28 - Days 1, 7, 14, 21, 28 - Days 1, 7, 14, 21, 28 - Days 1, 7, 14, 21, 28 - Days 1 & 21 - Days 1 & 21 - Days 7 & 28 LTMP secondary endpoints: - Days 28, 57, 85, 113, 141, 183 - Days 28, 57, 85, 113, 141, 183 - Days 28, 57, 85, 113, 141, 183 - Days 28, 57, 85, 113, 141, 183 - Day 28 & 183;Secondary end point(s): CP secondary endpoints: - The proportion of participants in whom S-K+ decreases by =0.5 mmol/L and who achieve normokalaemia during the first 72 hours - Time to first day achievement of normokalaemia - Absolute and percent change from baseline in S-K+ levels at all intervals of follow-up after dosing has been initiated - Time to decrease of = 0.5 mmol/L in S-K+ level - Proportion of participants per response category in Study Medication Palatability Assessment questionnaires (self reported or observer assessment) MP secondary endpoints: - Time from randomisation to relapse of hyperkalaemia in each treatment group - Proportion of participants within each treatment group who maintain normokalaemia per visit over the MP - Both absolute and percent change from baseline in S- K+ levels post dose during the MP and at any time point thereafter in each treatment group - Time to an increase in S-K+ concentration of =0.5 mmol/L in each treatment group - Number and percentage of days of normokalaemia - The difference in mean of all S-K+ values obtained during the MP in participants receiving either SZC or placebo - The number and percentage of participants with hypo- or hyperkalaemia in participants receiving either SZC or placebo - Change from baseline in S-Aldo to end of the MP - Change from baseline in plasma electrolytes (including bicar | — |
Countries
Canada, Poland, Romania, Russian Federation, Ukraine, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed