A Study in Children With Hyperkalaemia Between Birth and <18 Years of Age to Evaluate Doses of Sodium Zirconium Cyclosilicate (SZC) for Correction of Hyperkalaemia and Effectiveness of Same Dose to Maintain Normokalaemia.

• Status: Recruiting
• Trial end date: 2023-12-29
• Target enrollment: 0
• Participant gender: All

Summary

Sodium zirconium cyclosilicate has been shown to be effective and safe in adults for the treatment of hyperkalaemia, and therefore it is expected to be beneficial in children. This study will evaluate the efficacy, safety and tolerability of sodium zirconium cyclosilicate for the treatment of hyperkalaemia in children <18 years of age.

Primary 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 on achieving normokalaemia during the CP.

Overall design:

Approximately 140 participants will be enrolled at approximately 45 sites in locations including but not limited to Europe and North America for this study.

Treatment will include 3 phases: the CP, MP, and LTMP. Participants from 2 to <18 years are eligible to participate in all phases of the study. Participants <2 years of age will be included in the first 2 phases, namely the CP and the MP.

During the study, participants are recommended to be fasting prior to any visit pre-dose laboratory testing. All laboratory tests are taken pre-dose except select post dose K+ values during the CP. Electrocardiograms are to be taken prior to dosing. On visit days, the study treatment is to be taken at the site (during the CP this pertains only to the morning dose). For participants with diabetes, K+ measurements should be performed prior to insulin administration where possible.

For inclusion into the study i-STAT is used. For subsequent decisions on eligibility and determination of hyper and normokalaemia for entry into the MP and LTMP phases, local laboratory K+ is the determinant value.

Tolerability and safety will be assessed using AE reporting, results from laboratory testing, vital signs, physical examinations and ECG findings during the study. Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open ended non leading verbal questioning of the participant or participant's legal representative, as appropriate, is the preferred method to inquire about AE occurrences.

Participants are allowed to discontinue the study treatment and assessments at any time or at the discretion of the Investigator(s). The independent Data Monitoring Committee (iDMC) will monitor data during all phases of the study including DL evaluations.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Treatments: Benzocaine

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 <18 years of age.

3. Participants (including those receiving a stable peritoneal dialysis regimen) requiring long term treatment of hyperkalaemia (chronic hyperkalaemia) in the age cohort ≥2 years, and participants requiring either short- or long-term treatment for hyperkalaemia (acute and chronic hyperkalaemia) in the age cohort <2 years.

4. Participants must meet 1 of the following criteria for hyperkalaemia:

1. For participants ≥2 years of age, mean i STAT K+ level >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.

2. For participants <2 years of age, i STAT K+ level >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:

1. For participants aged 0 to ≤3 days after birth: <450 ms

2. For participants aged >3 days to <12 years: <440 ms

3. For participants ≥12 to <18 years: <450 ms (male), <460 ms (female) All QTcB values outside the reference values specified in the protocol should be manually re-measured and re-calculated, and if there is a difference in measurement between the automatic and manual ECG, the manual measurement should always be considered correct.

6. Ability to have repeated blood draws or effective venous catheterisation.

7. Females of childbearing potential must have a negative pregnancy test within 1 day prior to the first dose of SZC on CP Study Day 1 and sexually active females of childbearing potential must be using 2 forms of medically acceptable contraception with at least 1 being a barrier method

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 ischaemia (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, beta-adrenergic antagonists) and that would be more appropriately treated with other interventions (eg, fluid resuscitation, dose adjustments of medications).

6. Participants with transient iatrogenic hyperkalaemia (eg, due to treatment with tacrolimus or cyclosporine).

7. Participants treated with lactulose, rifaximin (XIFAXAN™), or other nonabsorbed antibiotics for hyperammonaemia within the last 7 days.

8. Participants treated with CPS, sodium polystyrene sulfonate (eg, KAYEXALATE™), or patiromer within the last 4 days.

9. Participants with a life expectancy of less than 3 months.

10. Participants who are known to have tested Human Immunodeficiency Virus (HIV) positive.

11. 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.

12. Known hypersensitivity or previous anaphylaxis to SZC or to components thereof.

13. Participants with cardiac arrhythmias that require immediate treatment.

14. Participants with a family history of long QT syndrome.

15. Participants on haemodialysis.

16. Participants with a history of bowel obstruction.

17. Participants with severe gastrointestinal disorder or major gastrointestinal surgery (eg, large bowel resection).

18. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

19. Previous treatment with SZC.

20. Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry.

21. Previous enrolment in the present study.

22. Females who are pregnant, breastfeeding, or planning to become pregnant.

23. 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.

24. 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.

25. 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.