An open-label study to assess safety and efficacy of SZC in paediatric patients with hyperkalaemia

JRCT ID: jRCT2031220173

Registered date:01/07/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Hyperkalaemia
• Date of first enrollment: 05/07/2022
• Target sample size: 3
• Countries of recruitment: Canada,Japan,United States,Japan,United Kingdom,Japan,Ukraine,Japan,Poland,Japan,Romania,Japan,China,Japan
• Study type: Interventional

Intervention(s)

Treatment includes 3 phases:CP,MP,LTMP.
Eligible participants with hyperkalaemia will enter CP receiving fixed dose of SZC three times daily (TID) for up to 3 days until normokalaemia.Within each cohort 2 to <18 years, initial participants will be allocated to dose level (DL) 5g TID. After higher DLs approval by iDMC,subsequent participants may be allocated in the CP to 10g TID and potentially 15g TID.Participants in 0 to <2 years cohort will be assigned to the same DL decided based on data from older cohorts.Those who achieve normokalaemia in the CP will enter a 28-day MP,which starts with once daily administration of the dose received TID in the CP.During MP,the Investigator is able to titrate the dose up or down in the range 2.5g to 15g body weight equivalent to maintain normokalaemia.For participants who, at the end of MP,are normokalaemic/hyperkalaemic without being on maximum dose,the MP is followed by option to continue in an LTMP where the same titration regimen is used as in MP

Outcome(s)

Primary Outcome

Correction phase (CP) primary objective: To evaluate the ability to achieve normokalaemia during the CP when initiating treatment with SZC of different dose levels in children with hyperkalaemia

28-day Maintenance Phase (MP) primary objective: To evaluate the ability to maintain normokalaemia during the MP when continuing SZC treatment in children achieving normokalaemia

Key inclusion & exclusion criteria

• Age minimum: >=
• Age maximum: < 18age old
• Gender: Both

Include 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 or more, 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:
For participants aged 2 years or more, Local Laboratory S-K+ level > 5.0 mmol/L, for participants aged 1 month to < 2 years, Local Laboratory S-K+ level > 6.0 mmol/L and for participants aged 0 to < 1 month, Local Laboratory S-K+ level > 6.5 mmol/L at Screening, measured 3 to 14 days prior to first dose of SZC on CP Study Day 1. This should also be confirmed prior to dosing on Day 1.

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 or less after birth: < 450 ms

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

c. For participants aged 12 or more 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 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:

a. 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.

b. Participants who are normokalaemic at the end of MP or hyperkalaemic and not on maximum dose.

c. Participants who would benefit from long-term treatment for their hyperkalaemia, as judged by the Investigator.

Exclude 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.

Related Information

• Primary Sponsor: Ageishi Yuji
• Secondary ID(s): NCT03813407