Patiromer for Treatment of Hyperkalaemia in Children Under 12 Years of Age

Study Overview
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Brief Summary
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A study to evaluate the pharmacodynamic effects, safety, and tolerability of patiromer in children under 12 years of age with hyperkalaemia

Official Title
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A 2-Part, Open-Label, Phase 2, Multiple Dose Study to Evaluate the Pharmacodynamic Effects, Safety, and Tolerability of Patiromer in Children Under 12 Years of Age With Hyperkalaemia (EMERALD2)

Conditions
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Hyperkalemia

Intervention / Treatment
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* Drug: Patiromer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The following inclusion criteria must be met for each subject: Paediatric subjects (<12 years of age) with hyperkalaemia at screening. Subject's age should not reach 12 years during the 28 days of the pharmacodynamic (PD)/dose-ranging period. Subject is able to receive regular external feeding and medication, including via tubes, e.g., percutaneous endoscopic gastrostomy (PEG or entero-gastric feeding tube). At screening/baseline, the results from 2 separate and consecutive potassium assessments using the same measurement method (whole blood, plasma, or serum) need to be above the age-appropriate ULN. If taking any renin-angiotensin aldosterone system inhibitors (RAASi), beta blockers, fludrocortisone, or diuretic medications, must be on a stable dose for at least 14 days prior to screening. Parent(s) or legally authorised representative(s) or another appropriate person delegated by the legally authorised representatives must be available to help the study-site personnel ensure follow-up; accompany the participant to the study site on each assessment day; accurately and reliably dispense investigational product as directed. Females of child bearing potential must be non-lactating, must have a negative pregnancy test at screening, and must have used an effective, acceptable form of contraception (e.g., abstinence) for at least 1 month before patiromer administration. Females of child bearing potential must agree to continue using contraception throughout the study and for 1 month after the last dose of patiromer. Exclusion Criteria: The following criteria exclude a subject from participating in this trial: Preterm birth infants with <37 weeks of gestation cannot be included in Cohort 3. Participants who due to their general condition, e.g., anaemia or low body weight, are not suitable to have blood volume withdrawn. Any of the following renal conditions: maintenance haemodialysis or peritoneal dialysis, renal artery stenosis, and acute kidney injury (defined by 2012 Kidney Disease Improving Global Outcomes) or a history of acute renal insufficiency in the past 3 months. Note: Chronic kidney disease (CKD) is not excluded. A history of or current diagnosis of a severe gastrointestinal (GI) diagnosis or surgery that could affect GI transit of the drug (delayed gastric emptying), such as a severe swallowing disorder, severe gastroesophageal reflux, uncorrected pyloric stenosis, intussusception, any other intestinal obstruction (e.g., Hirschsprung disease, chronic intestinal pseudo-obstruction, clinically significant postsurgical abdominal adhesions) or any gut-shortening surgical procedure prior to screening. Pre-gastric above-mentioned pathologies may be disregarded in case of existence of a PEG or entero-gastric feeding tube, as the PEG or entero-gastric feeding tube will serve for nutrition and investigational product administration. Active cancer, currently on cancer treatment, or history of cancer in the past 2 years (except for non-melanoma skin cancer). Recipient of any organ transplant requiring treatment with immunosuppressive therapy or scheduled for kidney transplant procedure during the first 28 days after Day 1. History of sudden infant death in a sibling (only for participants <2 years of age at screening). Use of the following medications if doses have not been stable for at least 14 days prior to screening or if doses are anticipated to change during the 4-week PD/ dose-ranging period: digoxin, bronchodilators, theophylline, heparins (including low molecular heparins), tacrolimus, mycophenolate mofetil, cyclosporine, trimethoprim, or cotrimoxazole. Use of any investigational product for an unapproved indication within 30 days prior to screening or within 5 half-lives, whichever is longer. Known hypersensitivity to patiromer or its components. If the child is being breastfed: There is suspicion of current alcohol or substance misuse/abuse in breastfeeding mother The breastfeeding mother is taking potassium supplements Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patiromer<br>4-week pharmacodynamic (PD)/dose-ranging period Cohort 1: 6 to <12 years of age Cohort 2: 2 to <6 years of age Cohort 3: 0 to <2 years of age); In Cohort 3, a minimum of 3 study participants will be assessed in the sub-group of 0 to <6 months and another 3 study participants in the sub-group 6 to <24 months of age. | Drug: Patiromer<br>* Patiromer will be given once daily; In Cohort 3, depending on the dose and the study participant's age, the total daily dose might be split<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in potassium levels (mmol/L) | May be measured as serum, plasma, whole blood, potassium | From baseline to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in potassium levels (mmol/L) | May be measured as serum, plasma, whole blood, potassium | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Occurrence of treatment-emergent adverse events (TEAEs) |  | Part 1: Day 1 up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to follow-up visit (Up to 54 weeks) | 
| Occurrence of serious adverse events (SAEs) |  | Part 1: Day 1 up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to follow-up visit (Up to 54 weeks) | 
| Change from baseline in resting heart rate (beats per minute) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in systolic blood pressure (mmHg) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in diastolic blood pressure (mmHg) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in body temperature (Celsius) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Number of patients with ECG abnormalities |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in chemistry laboratory evaluation: Calcium (mg/dL) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in chemistry laboratory evaluation: Phosphate (mg/dL) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in chemistry laboratory evaluation: Magnesium (mg/dL) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in chemistry laboratory evaluation: Potassium (mEq/L) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in chemistry laboratory evaluation: Sodium (mEq/L) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in chemistry laboratory evaluation: Creatinine (mg/dL) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in chemistry laboratory evaluation: Serum bicarbonate (mEq/L) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in chemistry laboratory evaluation: Blood urea nitrogen (mEq/L) |  | From baseline to Day 3, Day 7, Day 14, Day 28, and during Part 2: up to 52 weeks | 
| Change from baseline in haematology laboratory evaluation: White blood cells (10^9/L) |  | From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52) | 
| Change from baseline in haematology laboratory evaluation: Red blood cells count (10^12/L) |  | From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52) | 
| Change from baseline in haematology laboratory evaluation: Haemoglobin (10^12/L) |  | From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52) | 
| Change from baseline in haematology laboratory evaluation: Haematocrit (%) |  | From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52) | 
| Change from baseline in haematology laboratory evaluation: Platelet count (10^9/L) |  | From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52) | 
| Change from baseline in haematology laboratory evaluation: Blood fluoride (ng/mL) |  | From baseline to Day 7, Day 14, Day 28, and EoT visit for Part 2 (week 52) | 
| Occurrence of blood potassium below the lower limit of normal (LLN) (mmol/L) |  | Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks) | 
| Occurrence of blood potassium above the upper limit of normal (ULN) (mmol/L) |  | Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks) | 
| Occurrence of blood magnesium at levels specified in protocol (mmol/L) |  | Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks) | 
| Occurrence of abnormal clinical laboratory value findings | Occurrence of clinical laboratory value findings that are outside of normal range of the respective age for: serum calcium, phosphate, fluoride, creatinine, bicarbonate, and blood urea nitrogen levels | Part 1: Screening up to end of treatment (Day 28 ±3 Days); Part 2: Day 1 up to end of treatment (Up to 52 weeks) |