An Open-label Study to Assess Safety and Efficacy of SZC in Paediatric Patients With Hyperkalaemia

Launched by ASTRAZENECA · Jan 18, 2019

Keywords

ClinConnect Summary

This clinical trial is studying a medication called sodium zirconium cyclosilicate (SZC) to see how safe and effective it is for treating high potassium levels (hyperkalaemia) in children under 18 years old. High potassium can be a serious condition, and while SZC has been shown to work well in adults, researchers want to find out if it can help children too. The trial will include about 140 young participants across various sites in Europe and North America. Children will be grouped by age and treated with SZC for a few days, then monitored to see how well it lowers their potassium levels.

To be eligible for the trial, children must be between birth and 18 years old and have hyperkalaemia that needs treatment. Parents or guardians must provide consent, and older children may need to give their own agreement as well. Participants can expect to take SZC three times a day for a short period, followed by a maintenance phase where the dose may be adjusted as needed. Additionally, there will be options for long-term treatment if the child responds well to the initial therapy. This study is important because it could lead to better treatment options for children with this condition.

Gender

ALL

Eligibility 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 (for the study duration).
• • 3. Participants (including those receiving a stable peritoneal dialysis regimen for a minimum of 2 months) 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 the following criteria for hyperkalaemia: Please refer to the Table 6 in the protocol.
• • 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: \< 450 ms b. For participants aged \>3 days to \< 12 years: \< 440 ms c. For participants aged ≥ 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 (defined as a female with potential of becoming pregnant who has experienced her menarche) must have a negative pregnancy test within one 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 one being a barrier method
• 8. Optional open-label, LTMP only:
• • 1. Provision of written informed consent of the participant or legal representative, and informed assent from the participant (as appropriate) to take part in the LTMP.
• • 2. Participants who are normokalaemic at the end of MP or hyperkalaemic and not on maximum dose.
• • 3. Participants who would benefit from long-term treatment for their hyperkalaemia, as judged by the Investigator.
• 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).
• • 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 prior to first dose of study treatment.
• • 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 prior to first dose of study treatment 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. Judgement 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. 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.