Trial Evaluating the Efficacy and Safety of Patiromer in Chinese Subjects

Study Overview
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Brief Summary
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This is a multicentre, 2-part, single-blind, randomised, withdrawal, placebo-controlled study, that includes a 4-week patiromer treatment phase (Part A) followed by an 8-week randomised placebo-controlled withdrawal phase (Part B) and a 2-week follow-up period.

Detailed Description
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In Part A, participants who meet all eligibility criteria will initiate patiromer at an oral dose of 8.4 g (1 packet/day). The dose will be adjusted based on the serum potassium (sK+) levels. After the completion of part A, all the participants who meet the eligibility criteria for Part B will be randomised to receive patiromer or placebo. Participants will start Part B with the same dose of patiromer they were receiving at the end Part A. However, Patiromer dose may be up- or down-titrated based on sK+ levels. The primary objectives of the study are: Part A - To evaluate the efficacy of patiromer for the treatment of hyperkalemia in Chinese subjects. Part B - To evaluate the effect of withdrawing patiromer on sK+ control. To determine if the treatment with patiromer will result in continued use of renin-angiotensin-aldosterone system inhibitor (RAASi) medications.

Official Title
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A 2-Part, Single-Blind, Phase 3 Trial Evaluating the Efficacy and Safety of Patiromer for the Treatment of Hyperkalaemia in Chinese Subjects

Conditions
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Renal Insufficiency, Chronic, Hyperkalemia

Intervention / Treatment
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* Drug: Patiromer Powder for Oral Suspension (Part A)
* Drug: Placebo (Part B)
* Drug: Patiromer Powder for Orals Suspension (Part B)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese subjects at least 18 years of age. Chronic Kidney Disease (CKD) stage 3 and 4. Mean of 2 measurement of serum potassium higher than 5.0 and lower than 6.5 mEq/L at baseline. Subjects on any stable dose of at least 1 RAASi medication for at least 28 days before Day 0/baseline. If on antihypertensive medication, have a stable dose for 28 days before Day 0/baseline. Women of childbearing potential must agree to continue using contraception throughout the study and for 4 weeks after study completion. Exclusion Criteria: Any level of hyperkalemia at Day 0/baseline that, in the opinion of the Investigator, requires emergency intervention. Type 1 diabetes or Type 2 diabetes mellitus with glycated haemoglobin (Hb A1c) higher than 10.0% at screening/Part A baseline. History of acute renal insufficiency in the past 3 months prior to the beginning of the study. Diseases affecting the hearth muscle and heart's ability to pump blood around the body Major surgery including thoracic and cardiac within 3 months prior to the beginning of the study or anticipated need during study participation. Heart or kidney transplant recipient or anticipated need for transplant during study participation Diagnosis or treatment of a malignancy in the past 2 years before Day 0/baseline. Use of potassium supplements, bicarbonate or baking soda in the last 7 days prior to Day 0/baseline. Pregnant women or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2-part, single-blind, randomised withdrawal, placebo-controlled (Part B), parallel group study that includes a 4-week patiromer treatment phase (Part A) followed by an 8-week randomised placebo-controlled withdrawal phase (Part B).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Patiromer<br>Part A: 4-week, single-arm patiromer treatment phase (4 weeks) | Drug: Patiromer Powder for Oral Suspension (Part A)<br>* Participants initiate patiromer at an oral dose of 1 packet/day (8.4g/day as powder for suspension). The dose is adjusted ate the following visit based on local serum potassium (sK+) levels. The content of each packet should be mixed with water, apple or cranberry juice before administration.<br>|
| Placebo Comparator: Part B: Placebo<br>Part B: 8-week randomized, parallel group, placebo-controlled withdrawal phase | Drug: Placebo (Part B)<br>* Placebo is provided in packets, each containing 6 g of placebo as powder for suspension. Participants will take 1 packet per day, by mixing its content with water, apple or cranberry juice.<br>|
| Experimental: Part B: Patiromer<br>Part B: 8-week randomized, parallel group, placebo-controlled withdrawal phase | Drug: Patiromer Powder for Orals Suspension (Part B)<br>* Participants will continue to receive the same number of packets established during Part A, but dose may be up- or down titrated depending on sK+ levels. The content of each packet should be mixed with water, apple or cranberry juice before administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Change from baseline in the serum potassium (sK+) | Measured in milliequivalents per litre (mEq/L) | Week 4 | 
| Part B: Change from Week 4 in sK+ | Measured in mEq/L | The earlier of: Week 8 or the date when RAASi therapy is first decreased or discontinued | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Proportion of participants having an sK+ level between 3.8 and less than 5.1 mEq/L at Week 4 |  | Week 4 | 
| Part B: Proportion of participants taking any RAASi medication at Week 12 |  | Week 12 | 
| Part B: Proportion of subjects discontinuing/reducing RAASi medication due to hyperkalemia |  | From Week 4 to 2 weeks after the end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperkalemia, Chronic kidney disease