| CTRI Number |
CTRI/2025/02/080630 [Registered on: 14/02/2025] Trial Registered Prospectively |
| Last Modified On: |
13/02/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Other |
|
Public Title of Study
|
Research study with oral medication for children with high potassium |
|
Scientific Title of Study
|
An open-label study to assess safety and efficacy of SZC in paediatric patients
with hyperkalaemia |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 2018-001331-48 |
EudraCT |
| D9481C00001 V8.0 14Nov2023 |
Protocol Number |
| NCT03813407 |
ClinicalTrials.gov |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Shekhar Dawkhar |
| Designation |
Senior Director |
| Affiliation |
Fortrea Development India Private Limited |
| Address |
Fortrea Development India Private Limited,Building No.1,Unit No.601,Raheja Mindspace,Plot Nos. Gen/2/1/D/E/F at MIDCTTC
Industrial Area,Shiravane, Nerul,Navi Mumbai
Mumbai (Suburban)
MAHARASHTRA
400706
India |
| Phone |
7506653414 |
| Fax |
|
| Email |
shekhar.dawkhar@fortrea.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Shekhar Dawkhar |
| Designation |
Senior Director |
| Affiliation |
Fortrea Development India Private Limited |
| Address |
Fortrea Development India Private Limited,Building No.1,Unit No.601,Raheja Mindspace,Plot Nos. Gen/2/1/D/E/F at MIDCTTC
Industrial Area,Shiravane, Nerul,Navi Mumbai
Mumbai (Suburban)
MAHARASHTRA
400706
India |
| Phone |
7506653414 |
| Fax |
|
| Email |
shekhar.dawkhar@fortrea.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Shekhar Dawkhar |
| Designation |
Senior Director |
| Affiliation |
Fortrea Development India Private Limited |
| Address |
Fortrea Development India Private Limited,Building No.1,Unit No.601,Raheja Mindspace,Plot Nos. Gen/2/1/D/E/F at MIDCTTC
Industrial Area,Shiravane, Nerul,Navi Mumbai
Mumbai (Suburban)
MAHARASHTRA
400706
India |
| Phone |
7506653414 |
| Fax |
|
| Email |
shekhar.dawkhar@fortrea.com |
|
|
Source of Monetary or Material Support
|
| Fortrea Development India Private Limited,Building No. 1, Unit No. 601, Raheja Mindspace,Plot Nos. Gen/2/1/D/E/F at MIDCTTC Industrial Area, Shiravane, Nerul,Navi Mumbai, Maharashtra 400706,India |
|
|
Primary Sponsor
|
| Name |
AstraZeneca AB |
| Address |
151 85 Sodertalje, Sweden |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Fortrea Development India Private Limited |
Building No. 1, Unit No. 601, Raheja Mindspace,Plot Nos. Gen/2/1/D/E/F at MIDCTTC Industrial Area, Shiravane, Nerul,Navi Mumbai, Maharashtra 400706,India |
|
|
Countries of Recruitment
|
Brazil
Canada
China
Germany
India
Japan
Poland
Romania
Spain
Ukraine
United Kingdom
United States of America |
|
Sites of Study
|
| No of Sites = 3 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Sandip Kumar Panda |
All India Institute of Medical Sciences |
Sijua Patrapada, Bhubaneswar-751019, Odisha
Khordha
ORISSA |
9626801175
nephro_sandip@aiimsbhubaneswar.edu.in |
| Dr Sidharth Kumar Sethi |
Medanta-The Medicity |
CH Baktawar Singh Road, Islampur Colony, Sector-38, Gurugram-122001, Haryana
Gurgaon
HARYANA |
9868306235
sidsdoc@gmail.com |
| Dr Kanav Anand |
Sir Ganga Ram Hospital |
Sir Ganga Ram Hospital Marg, Rajinder Nagar, New Delhi-110060
New Delhi
DELHI |
9818664448
Clindatacare@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 3 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee AIIMS Bhubaneswar |
Submittted/Under Review |
| Medanta Institutional Ethics Committee |
Approved |
| Sir Ganga Ram Hospital Ethics Committee |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: E888||Other specified metabolic disorders, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Not Applicable |
Not Applicable |
| Intervention |
Sodium Zirconium Cyclosilicate |
Drug: Sodium Zirconium Cyclosilicate (SZC) Reduced Dose Level
Sodium Zirconium Cyclosilicate (SZC) Dose: Paediatric dose based on body weight equivalent to an adult 2.5 g
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
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
Drug: Sodium Zirconium Cyclosilicate (SZC) Dose Level 3 (DL3)
Sodium Zirconium Cyclosilicate (SZC) Paediatric dose based on body weight equivalent to an adult 15 g
Drug: Sodium Zirconium Cyclosilicate (SZC) Dose During 28 Day Maintenance Phase
A 28-day period during which SZC is administered orally once daily (QD) to maintain normokalaemia. A dose titration regimen starting with QD administration of the dose of SZC the participants received TID in the CP will be studied in the MP and continued in the LTMP. The maximum dose that can be used is the calculated body weight equivalent to the 15 g adult dose. The total duration of intervention is 88 months i.e 7 years 33 months. |
|
|
Inclusion Criteria
|
| Age From |
0.00 Year(s) |
| Age To |
18.00 Year(s) |
| Gender |
Both |
| Details |
1.Provision of written informed consent of the participant or legal representative, and informed assent from the participant.
2.Female or male from birth to less than 18 years of age.
3.Participants requiring long-term treatment of hyperkalaemia in the age cohort equal to more than 2 years, and participants requiring either short- or long-term treatment for hyperkalaemia in the age cohort less than 2 years.
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 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. |
|
| ExclusionCriteria |
| Details |
1.Neonates with a gestational age less than 37 weeks at birth or a birth weight less than 2500 g.
2.Term and preterm neonates with suspected conditions predisposing them to intestinal ischaemia
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 and that would be more appropriately treated with other interventions.
6.Participants with transient iatrogenic hyperkalaemia.
7.Participants treated with lactulose, rifaximin, or other nonabsorbed antibiotics for hyperammonaemia within the last 7 days.
8.Participants treated with CPS, sodium polystyrene sulfonate, 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 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.
18.Involvement in the planning and/or conduct of the study.
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 within 2 weeks prior to enrolment the participant cannot be enrolled in the study. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
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. |
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 MP primary endpoint: Serum potassium (S-K+) value within normokalaemia range (yes/no) at each of the last two scheduled visits in the MP. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| 1.To evaluate the change in S-K in children treated with SZC |
1.All phases secondary endpoint: S-K level at each scheduled visit. |
| 2.MP secondary objectives: To evaluate change in serum aldosterone levels in children treated with SZC during the MP |
2.MP secondary endpoints: Change in serum aldosterone levels from baseline to Week 3 of the MP |
| 3.MP Secondary objective: To evaluate change in serum electrolytes, spot urinary pH and urinary electrolytes levels in children treated with SZC during the MP |
3.Change in serum electrolytes, and spot urinary pH and urinary electrolytes from baseline to week 3 of the MP |
| 4.Long-term MP secondary objectives: To evaluate the ability of maintaining normokalaemia in children treated with SZC during the LTMP |
4.LTMP secondary endpoints: S-K value within normokalaemia range at each scheduled visit in the LTMP |
|
|
Target Sample Size
|
Total Sample Size="140"
Sample Size from India="24"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
28/02/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
02/04/2019 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="2"
Months="8"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
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. Approximately 140 participants will enter CP at approximately 46 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. Enrolment will start in 2 cohorts, ages 6 to < 12 years and 12 to < 18 years. After review of accumulated data, the independent Data Monitoring Committee (iDMC) will recommend whether to open enrolment in the ages 2 to < 6 years cohort and later in the ages 0 to < 2 years cohort. All eligible participants with hyperkalaemia will enter an open-label Correction Phase (CP) receiving a fixed dose of SZC three times daily (TID) for up to 3 days until normokalaemia is achieved. Within each age cohorts 2 to < 18 years, initial participants will be allocated to the dose level (DL) based on body weight equivalent to an adult 5 g TID. After recommendation of higher DLs by the iDMC, subsequent participants may be allocated in the CP to on body weight equivalent to an adult 10 g TID and then potentially on body weight equivalent to an adult 15 g TID. All participants in the ages 0 to < 2 years cohort will be assigned to the same DL which will be decided based on data from older age cohorts. Participants who successfully achieve normokalaemia in the CP will enter a 28-day open-label Maintenance Phase (MP), which will be initiated 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 2.5 g to 15 g body weight equivalent to maintain normokalaemia. For participants who, at the end of MP, are normokalaemic or hyperkalaemic without being on maximum dose, the MP is followed by the option to continue the study in a long term maintenance phase (LTMP) where the same titration regimen is used as in MP. |