Pharmacodynamic & Safety of Patiromer in Children & Adolescents (2-<18 Yrs) With Chronic Kidney Disease and Hyperkalemia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the change in serum potassium levels from start of treatment to Day 14, when patiromer is administered at different doses, once daily, in children 2 - < 18 years of age with chronic kidney disease (CKD) and hyperkalemia (too much potassium in the blood). Another purpose of the study is to evaluate the safety and tolerability of patiromer in children 2 - < 18 years of age with CKD and hyperkalemia.

Detailed Description
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Up to 54 subjects, 2 - < 18 years of age with CKD (estimated glomerular filtration rate [eGFR] < 90 mL/min/1.73 m2 ) and hyperkalemia (two potassium measurements of 5.1 to < 6.5 mEq/L performed on separate days) will be enrolled in this open-label, multiple-dose, Phase 2 study. The study will include two treatment phases: Pharmacodynamic (PD; drug effect on potassium) / Dose Finding Phase consisting of the initial 14-day dose finding period followed by an up to 5.5-month Long-Term Treatment Phase for a total study participation duration for individual subjects of up to 6.5 months (includes a 2 week follow up period).

Official Title
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A Phase 2, Open-Label, Multiple Dose Study to Evaluate the Pharmacodynamic Effects, Safety, and Tolerability of Patiromer for Oral Suspension in Children and Adolescents 2 to < 18 Years of Age With Chronic Kidney Disease and Hyperkalemia

Conditions
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Hyperkalemia

Intervention / Treatment
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* Drug: Patiromer
* Drug: Patiromer
* Drug: Patiromer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written assent (when applicable) and written informed consent by a legally authorized representative provided prior to participation in the study Age 2 - <18 years old CKD defined by the estimated glomerular filtration rate (eGFR) <90 mL/min/1.73m2, including renal transplant subjects, based on local creatinine measurement at screening Two potassium measurements of 5.1 to < 6.5 mEq/L performed on separate days In the opinion of the study doctor, is expected to require treatment for hyperkalemia for at least 6 month If taking any renin-angiotensin-aldosterone system inhibitors (RAASi) beta blockers or diuretic medications, must be on a stable dose for at least 28 days prior to Screening Negative pregnancy test in females of child-bearing potential Exclusion Criteria: Pseudohyperkalemia due to hemolysis or to abnormally high numbers of platelets (>500,000/mm3), leukocytes (>70,000/mm3), or erythrocytes (hematocrit >55%) at Screening based on results obtained locally Evidence of potassium-related electrocardiogram (ECG) changes at Screening Any of the following kidney conditions: maintenance hemodialysis or peritoneal dialysis, renal artery stenosis, and acute kidney injury or a history of acute renal insufficiency in the past 3 months Severe disorder of stomach or intestines including surgery that could affect gastrointestinal transit of the drug Increased liver enzymes (ALT, AST > 3 times upper limit of normal) at Screening Active cancer, currently on cancer treatment or history of cancer in the past 2 years (except for non-melanoma skin cancer) Heart or liver transplant, or anticipated need for transplant during the study treatment period including a scheduled kidney transplant recipient. (Note: patients currently on a kidney transplant wait list are not excluded unless there is an identified donor). Alcohol abuse or substance use disorder within 1 year of Screening Subjects currently being treated with or having taken any one of the following medications (includes resins) in the 7 days prior to Screening: sodium or calcium polystyrene sulfonate, drospirenone Use of certain medications that can affect blood potassium levels if doses have not been stable for at least 14 days prior to Screening or if doses are anticipated to change during the 14-day PD / Dose Finding Phase Use of investigational product within 30 days of screening or within 5 half-lives, whichever is longer Known hypersensitivity to patiromer or its components In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, or serious intercurrent illness that would significantly decrease study compliance or jeopardize the safety of the subject or potentially affect the quality of the data

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Patiromer for age 12 to < 18 years | Drug: Patiromer<br>* 4.2 g/day, 8.4 g/day and 16.8 g/day<br>* Other names: RLY5016 for Oral Suspension;|
| Experimental: Cohort 2<br>Patiromer for age 6 to < 12 years | Drug: Patiromer<br>* 2 g/day, 4 g/day and 8 g/day<br>* Other names: RLY5016 for Oral Suspension;|
| Experimental: Cohort 3<br>Patiromer for age 2 to < 6 years | Drug: Patiromer<br>* 1 g/day, 2 g/day and 4 g/day<br>* Other names: RLY5016 for Oral Suspension;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Potassium Levels |  | from Baseline to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With Serum Potassium Levels in the Range of 3.8 - 5.0 mEq/L | Day 14: Initial PD / Dose Finding Phase. Week 26: Long-Term Treatment Phase. | Day 14 and Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment of Hyperkalemia, Hyperkalemia, Potassium, Chronic Kidney Disease