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Trial record 32 of 119 for:    ZIRCONIUM

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.

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ClinicalTrials.gov Identifier: NCT03813407
Recruitment Status : Recruiting
First Posted : January 23, 2019
Last Update Posted : September 27, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief 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 dose levels on achieving normokalaemia during the CP.

Overall design:

Approximately 100 subjects will be enrolled at approximately 40 sites in locations including but not limited to Europe and North America for this study.

This study will enrol males and females aged birth to <18 years with hyperkalaemia, except neonates with a gestational age less than 30 weeks or a birth weight less than 1500 g.

All subjects are eligible for open-label treatment with SZC during the Correction Phase, and subjects aged 2 to <18 years who are eligible to participate in the Maintenance Phase will be randomised in a 1:1 ratio to double-blinded treatment with SZC or matching placebo comparator. Subjects aged <2 years who require continuing treatment will participate in an open-label Maintenance Phase. Only subjects aged 2 to <18 years may continue to the optional open-label Long-Term Maintenance Phase.

Treatment will be stratified by the following age cohorts during the study:

  • 12 to <18 years of age
  • 6 to <12 years of age
  • 2 to <6 years of age
  • 0 to <2 years of age, except neonates with a gestational age less than 30 weeks or a birth weight less than 1500 g. During the dose escalation period in the CP, treatment will first be initiated in the oldest age cohort (12 to <18 years). The age cohort 6 to <12 years will start as soon as study drug is available. Dosing may then be started sequentially in the younger age cohorts, depending on the safety and efficacy data during the CP in the older cohorts.

Data Monitoring Committee:

An independent Data Monitoring Committee will be utilised for this study to evaluate emerging afety data during the dose escalation part of the study


Condition or disease Intervention/treatment Phase
Hyperkalaemia Drug: Sodium Zirconium Cyclosilicate (SZC) Reduced Dose Level Drug: Sodium Zirconium Cyclosilicate (SZC) Dose Level 1 (DL1) Drug: Sodium Zirconium Cyclosilicate (SZC) Dose Level 2 (DL2) Drug: Sodium Zirconium Cyclosilicate (SZC) Dose Level 3 (DL3) Drug: Sodium Zirconium Cyclosilicate (SZC) Dose During 28 Day Maintenance Phase Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This study will enrol males and females aged birth to <18 years with hyperkalaemia, except neonates with a gestational age less than 30 weeks or a birth weight less than 1500 g. All subjects are eligible for open-label treatment with SZC during the Correction Phase, and subjects aged 2 to <18 years who are eligible to participate in the Maintenance Phase will be randomised in a 1:1 ratio to double-blinded treatment with SZC or matching placebo comparator. Subjects aged <2 years who require continuing treatment will participate in an open-label Maintenance Phase. Only subjects aged 2 to <18 years may continue to the optional open-label Long-Term Maintenance Phase.

Treatment will be stratified by the following age cohorts during the study:

  • 12 to <18 years of age
  • 6 to <12 years of age
  • 2 to <6 years of age
  • 0 to <2 years of age, except neonates with a gestational age less than 30 weeks or a birth weight less than 1500 g.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: This study consist of double blinded treatment as well as open label treatment.
Primary Purpose: Treatment
Official Title: A Phase 3, Dose-Escalating Study in Children With Hyperkalaemia Between Birth and <18 Years of Age to Evaluate Increasing Doses of Sodium Zirconium Cyclosilicate (SZC) Given Three Times Daily for the Correction of Hyperkalaemia and the Effectiveness of the Same Dose of SZC Given Once Daily to Maintain Normokalaemia Among Those Requiring Continuous Treatment.
Actual Study Start Date : April 2, 2019
Estimated Primary Completion Date : July 13, 2021
Estimated Study Completion Date : July 13, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Active Arm ( Sodium Zirconium Cyclosilicate SZC)

This study will enrol males and females aged birth to <18 years with hyperkalaemia, except neonates with a gestational age less than 30 weeks or a birth weight less than 1500 g.

All subjects are eligible for open-label treatment with SZC during the Correction Phase, and subjects aged 2 to <18 years who are eligible to participate in the Maintenance Phase will be randomised in a 1:1 ratio to double-blinded treatment with SZC or matching placebo comparator.

Drug: Sodium Zirconium Cyclosilicate (SZC) Reduced Dose Level

Sodium Zirconium Cyclosilicate (SZC) Dose:

To be considered by the iDMC in consultation with the Sponsor, if de-escalation is indicated by evaluation of safety/tolerability data


Drug: Sodium Zirconium Cyclosilicate (SZC) Dose Level 1 (DL1)
Sodium Zirconium Cyclosilicate (SZC)Paediatric dose based on body weight equivalent to an adult 5 g TID (CP) or QD (MP/LTMP) dose

Drug: Sodium Zirconium Cyclosilicate (SZC) Dose Level 2 (DL2)
Sodium Zirconium Cyclosilicate (SZC) Paediatric dose based on body weight equivalent to an adult 10 g TID (CP) or QD (MP/LTMP) dose

Drug: Sodium Zirconium Cyclosilicate (SZC) Dose Level 3 (DL3)
Sodium Zirconium Cyclosilicate (SZC) To be considered by the iDMC in consultation with the Sponsor if further dose escalation is indicated by evaluation of safety/tolerability and efficacy data

Drug: Sodium Zirconium Cyclosilicate (SZC) Dose During 28 Day Maintenance Phase
A 28-day MP during which Sodium Zirconium Cyclosilicate ( SZC) or placebo is administered in randomised, double-blind manner orally once daily (QD) to maintain normokalaemia in subjects from 2 to <18 years. Subjects will be randomised in a 1:1 ratio to either SZC or placebo treatment.

Placebo Comparator: Placebo Arm
To compare the effect of SZC vs placebo on maintaining normokalaemia during the MP.28-day maintenance phase (MP) primary endpoint (primary analysis endpoint): The proportion of subjects in whom normokalaemia can be maintained throughout the MP.
Drug: Sodium Zirconium Cyclosilicate (SZC) Dose During 28 Day Maintenance Phase
A 28-day MP during which Sodium Zirconium Cyclosilicate ( SZC) or placebo is administered in randomised, double-blind manner orally once daily (QD) to maintain normokalaemia in subjects from 2 to <18 years. Subjects will be randomised in a 1:1 ratio to either SZC or placebo treatment.




Primary Outcome Measures :
  1. 28-day maintenance phase (MP) primary endpoint (Primary Analysis Endpoint): The proportion of subjects in whom normokalaemia can be maintained throughout the MP. [ Time Frame: 28 Days ]
    The proportion of subjects in whom normokalaemia can be maintained throughout the Maintenance phase.

  2. Correction phase (CP) primary endpoint: The proportion of subjects in whom serum K decreases by ≥0.5 mmol/L and who achieve normokalaemia at (by or before) 24, 48 and 72 hours during Correction Phase. [ Time Frame: 24, 48 and 72 Hours ]
    The proportion of subjects in whom serum K decreases by ≥0.5 mmol/L and who achieve normokalaemia at (by or before) 24, 48 and 72 hours during Correction Phase.


Secondary Outcome Measures :
  1. Correction Phase secondary endpoints The proportion of subjects in whom serum K decreases by ≥0.5 mmol/L and who achieve normokalaemia during the first 72 hours [ Time Frame: 72 hours ]
    The proportion of subjects in whom serum K decreases by ≥0.5 mmol/L and who achieve normokalaemia during the first 72 hours.

  2. Maintenance Phase secondary endpointsTime from randomization to relapse of hyperkalaemia.: [ Time Frame: 28 Days ]
    Time from randomization to relapse of hyperkalaemia (return to serum K level >5.0 mmol/L for subjects 2 to <18 years and >6.0 mmol/L for subjects <2 years) in each treatment group

  3. Maintenance Phase Secondary endpointProportion of subjects within each treatment group who maintain normal serum K levels . [ Time Frame: 28 days ]
    Proportion of subjects within each treatment group who maintain normal serum K levels (defined as serum K of ≥3.5 mmol/L and ≤5.0 mmol/L for subjects aged 2 to <18 years and serum K of ≥3.5 mmol/L and ≤6.0 mmol/L for subjects <2 years) per visit over the MP

  4. Maintenance Phase Secondary End Poin. Absolute change from base line in serum K levels post dose during MP and at any time point thereafter in each treatment group. [ Time Frame: 28 days ]
    Absolute change from baseline in serum K levels post dose during the MP and at any time point thereafter in each treatment group

  5. Maintenance Phase Secondary End PoinTime to an increase in serum K concentration of 0.5 mmol/L in each treatment group. [ Time Frame: 28 Days ]
    Time to an increase in serum K concentration of 0.5 mmol/L in each treatment group

  6. Maintenance Phase Secondary End poinThe difference in mean of all serum K values obtained during the MP in subjects receiving either SZC or placebo. [ Time Frame: 28 Days ]
    The difference in mean of all serum K values obtained during the MP in subjects receiving either SZC or placebo

  7. Maintenance Phase Secondary End Point Percentage of subjects with hypokalaemia in subjects receiving either SZC or Placebo [ Time Frame: 28 Days ]
    The percentage of subjects with hypokalaemia (<3.0 mmol/L) in subjects receiving either SZC or placebo

  8. Maintenance Phase Secondary End pointChange from baseline in serum aldosterone (S-Aldo) to end of the MP [ Time Frame: 28 Days ]
    Change from baseline in serum aldosterone (S-Aldo) to end of the MP

  9. Maintenance Phase Secondary EndpoinProportion of patients per response category in Study Medication Palatability Assessment questionnaires. [ Time Frame: 28 Days ]
    Proportion of patients per response category in Study Medication Palatability Assessment questionnaires (self reported or observer assessment)

  10. Maintenance Phase Secondary End poinPercentage of days of normokalaemia. [ Time Frame: 28 Days ]
    Percentage of days of normokalaemia

  11. Long Term Maintenance Phase secondary endpointsProportion of subjects in whom normokalaemia can be maintained over the LTMP. [ Time Frame: 22 Weeks ]
    Proportion of subjects in whom normokalaemia can be maintained over the LTMP.

  12. Long Term Maintenance Phase Secondary End Proportion of subjects who needed dose escalation to higher dose levels during the LTMP. [ Time Frame: 22 weeks ]
    Proportion of subjects who needed dose escalation to higher dose levels during the LTMP

  13. Long Term Maintenance Phase Secondary End PointProportion of subjects who needed dose deescalation to lower dose levels during the LTMP [ Time Frame: 22 Weeks ]
    Proportion of subjects who needed dose deescalation to lower dose levels during the LTMP

  14. Long Term Maintenance Phase Secondary End Point Percentage of subjects with hypokalaemia during LTMP [ Time Frame: 22 Weeks ]
    The percentage of subjects with hypokalaemia- (<3.0 mmol/L) during the LTMP.

  15. Long Term Maintenance Phase Secondary End PoinProportion of patients per response category in Study Medication Palatability Assessment. [ Time Frame: 22 weeks ]
    Proportion of patients per response category in Study Medication Palatability Assessment questionnaires (self reported or observer assessment)

  16. Correction Phase Secondary enpoints Time to first day achievement of normokalaemia [ Time Frame: From date of first dose in the Correction Phase to date of first date of normokalaemia, or date of censoring as applicable, assessed up to 72 hours ]
    Time to first day achievement of normokalaemia

  17. Correction Phase Secondary Endpoint Absolute change from baseline in serum K levels at all intervals of follow-up [ Time Frame: At baseline and at 24, 48 and 72 hours ]
    Absolute change from baseline in serum K levels at all intervals of follow-up after dosing has been initiated

  18. Correction Phase Secondary End Point Time to decrease of 0.5 mmol/L in serum K level [ Time Frame: From date of first dose in the CP to date of first date of decrease of ≥0.5 mmol/L, or date of censoring as applicable, assessed up to 72 hours" ]
    Time to decrease of 0.5 mmol/L in serum K level

  19. Correction Phase Secondary EndpointProportion of patients per response category in Study Medication Palatability Assessment questionnaires. [ Time Frame: At baseline and 48 hours ]
    Proportion of patients per response category in Study Medication Palatability Assessment questionnaires (self reported or observer assessment)

  20. Maintenance Phase Secondary Endpoint Change from Baseline in Sodium (plasma electrolytes.) [ Time Frame: 28 Days ]
    Change from Baseline to Visit 7 For Sodium (Plasma Electrolyte)

  21. Maintenance Phase Secondary Endpoint Change from Baseline in Potassium (plasma electrolytes.) [ Time Frame: 28 Days ]
    Change from Baseline to Visit 7 For Potassium (Plasma Electrolyte)

  22. Maintenance Phase Secondary Endpoint Change from Baseline in Calcium ( plasma electrolytes.) [ Time Frame: 28 Days ]
    Change from Baseline to Visit 7 For Calcium (Plasma Electrolyte)

  23. Maintenance Phase Secondary Endpoint Change from Baseline in Phosphrous ( plasma electrolytes.) [ Time Frame: 28 Days ]
    Change from Baseline to Visit 7 For Phosphrous (Plasma Electrolyte)

  24. Maintenance Phase Secondary Endpoint Change from Baseline in Megnesium ( plasma electrolytes.) [ Time Frame: 28 Days ]
    Change from Baseline to Visit 7 For Megnesium (Plasma Electrolyte)

  25. Correction Phase Secondary Endpoint Percent change from baseline in serum K levels at all intervals of follow up [ Time Frame: At Baseline and at 24, 48 and 72 Hours ]
    Percentage change from base in serum K levels at all intervals of follow up after dosing has been initiated.

  26. percent change from baseline in serum K levels post dose during the MP and at any time point thereafter in each treatment group [ Time Frame: 28 Days ]
    Percent change from baseline in serum K levels post dose during the MP and at any time point thereafter in each treatment group

  27. The percentage of subjects with hyperkalaemia (>6.0 mmol/L) in subjects receiving either SZC or placebo. [ Time Frame: 28 Days ]
    The percentage of subjects with hyperkalaemia (>6.0 mmol/L) in subjects receiving either SZC or placebo

  28. Maintenance phase secondary end point change from baseline in Bicarbonate (plasma electrolytes) [ Time Frame: 28 days ]
    Change from Baseline to Visit 7 For Bicarbonate (plasma electrolytes)

  29. Maintenance Phase Secondary Endpoint Change from Baseline in Spot Urine PH [ Time Frame: 28 Days ]
    Change from Baseline to Visit 7 For Spot Urine PH.

  30. Maintenance Phase Secondary End Point percentage of days of normokalaemia [ Time Frame: 28 Days ]
    Percentage of days of normokalaemia.

  31. Long Term Maintenance Phase Secondary End Point Percentage of subjects with hyperkalaemia during LTMP. [ Time Frame: 22 Weeks ]
    The percentage of Subjects with hyperkalaemia (>6.0 mmol/L) during the LTMP.

  32. Maintenance Phase Secondary Endpoint Change from Baseline in Spot Urine Sodium [ Time Frame: 28 Days ]
    Change from Baseline to Visit 7 For Spot urine Sodium.

  33. Maintenance Phase Secondary Endpoint Change from Baseline in Spot Urine Potassium [ Time Frame: 28 Days ]
    Change from Baseline to Visit 7 For Spot urine Potassium.

  34. Maintenance Phase Secondary Endpoint Change from Baseline in Spot Urine Bicarbonate [ Time Frame: 28 Days ]
    Change from Baseline to Visit 7 For Spot urine Bicarbonate.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of written informed consent of the subject or legal representative, and informed assent from the subject (as appropriate) as described in Appendix A 3.
  2. Female or male from birth to <18 years of age.
  3. Subjects requiring long-term treatment of hyperkalaemia (chronic hyperkalaemia) in the age cohort ≥2 years, and subjects requiring either short- or long-term treatment for hyperkalaemia (acute and chronic hyperkalaemia) in the age cohort <2 years.
  4. Subjects must meet 1 of the following criteria for hyperkalaemia:

    1. For subjects ≥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 subjects <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.

Using digital ECG, QT interval corrected by Bazett's method (QTcB) must meet the age-appropriate parameters at Screening:

  1. For subjects aged 0 to ≤3 days after birth: <450 ms
  2. For subjects aged >3 days to <12 years: <440 ms
  3. For subjects ≥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 catheterization. 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 <30 weeks or a birth weight <1500 g.

    2. Subjects with pseudohyperkalaemia caused by excessive fist clenching to enable venepuncture, by haemolysed blood specimens, or by severe leukocytosis or thrombocytosis. 3. Subjects with hyperkalaemia due to soft-tissue damage from crush injury or burns.

    4. Subjects treated with lactulose, rifaximin (XIFAXAN™), or other nonabsorbed antibiotics for hyperammonaemia within the last 7 days. 5. Subjects treated with calcium polystyrene sulfonate (CPS), sodium polystyrene sulfonate (e.g., KAYEXALATE™), or patiromer within the last 4 days. 6. Subjects with a life expectancy of less than 3 months. 7. Subjects who are known to have tested Human Immunodeficiency Virus (HIV) positive. 8. Presence of any condition which, in the opinion of the Investigator, places the subject at undue risk or potentially jeopardises the quality of the data to be generated.

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

    10. Subjects with cardiac arrhythmias that require immediate treatment. 11. Subjects with a family history of long QT syndrome. 12. Subjects on dialysis to exclude subjects requiring acute or chronic renal replacement therapy. 13. Subjects with a history of bowel obstruction. 14. Subjects with severe gastrointestinal disorder or major gastrointestinal surgery (e.g., large bowel resection). 15. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 16. Previous treatment with SZC. 17. Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry. 18. Previous enrolment in the present study. 19. Females who are pregnant, breastfeeding, or planning to become pregnant. 20. Judgment by the Investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03813407


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, California
Research Site Not yet recruiting
Los Angeles, California, United States, 90095-1725
United States, Kentucky
Research Site Not yet recruiting
Louisville, Kentucky, United States, 40202
United States, Missouri
Research Site Not yet recruiting
Saint Louis, Missouri, United States, 63104-1095
United States, New Jersey
Research Site Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Research Site Not yet recruiting
Stony Brook, New York, United States, 11794
United States, Texas
Research Site Withdrawn
Dallas, Texas, United States, 75235
Canada, Alberta
Research Site Not yet recruiting
Edmonton, Alberta, Canada, T6G 1C9
Italy
Research Site Withdrawn
Milano, Italy, 20122
Poland
Research Site Not yet recruiting
Bialystok, Poland, 15-089
Research Site Not yet recruiting
Krakow, Poland, 30-663
Romania
Research Site Not yet recruiting
Bucuresti, Romania, 077120
Research Site Not yet recruiting
Bucuresti, Romania, 22328
Research Site Not yet recruiting
Cluj-Napoca, Romania, 400177
Research Site Not yet recruiting
Targu Mures, Romania, 540136
Russian Federation
Research Site Withdrawn
Moscow, Russian Federation, 107014
Research Site Not yet recruiting
Samara, Russian Federation, 443095
Ukraine
Research Site Not yet recruiting
Kharkiv, Ukraine, 61075
Research Site Not yet recruiting
Sumy, Ukraine, 40031
Research Site Not yet recruiting
Zaporizhzhya, Ukraine, 69063
United Kingdom
Research Site Recruiting
Glasgow, United Kingdom, G51 4TF
Research Site Not yet recruiting
Manchester, United Kingdom, M13 9WL
Research Site Recruiting
Nottingham, United Kingdom, NG7 2UH
Sponsors and Collaborators
AstraZeneca

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03813407     History of Changes
Other Study ID Numbers: D9481C00001
First Posted: January 23, 2019    Key Record Dates
Last Update Posted: September 27, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Not Yet Decided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
sodium zirconium cyclosilicate
Hyperkalaemia in children
Additional relevant MeSH terms:
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Hyperkalemia
Water-Electrolyte Imbalance
Metabolic Diseases
Benzocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents