A Two-Part, Single-Blind, Phase 3 Study Evaluating the Efficacy and Safety of Patiromer for the Treatment of Hyperkalemia (OPAL)

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy and safety of patiromer (investigational drug) in the treatment of hyperkalemia (high serum potassium). The study also evaluated the effect of withdrawing patiromer treatment and assessed whether chronic treatment with patiromer prevented the recurrence of hyperkalemia. The safety of patiromer treatment was also evaluated.

Detailed Description
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There were two parts in the study, Part A and Part B. Part A was an assessment of 4 weeks of dosing with patiromer in the treatment of hyperkalemia; Part B was a randomized, placebo-controlled, 8-week assessment of the withdrawal of patiromer in participants with a baseline serum potassium at the beginning of Part A ≥ 5.5 mEq/L who responded to the 4 weeks of treatment with patiromer during Part A. All participants received patiromer during Part A; Part B participants were randomized to continue patiromer or switch to placebo. Total study participation was up to 14 weeks (including up to 2 weeks of follow up). The dose of patiromer could be titrated based on participant's serum potassium response.

Official Title
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A Two-Part, Single-Blind, Phase 3 Study Evaluating the Efficacy and Safety of Patiromer for the Treatment of Hyperkalemia

Conditions
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Chronic Kidney Disease (CKD), Hyperkalemia (HK)

Intervention / Treatment
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* Drug: Patiromer
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ages 18 - 80 Chronic kidney disease (CKD) - eGFR 15 to < 60 mL/min/1.73m2 at screening Hyperkalemia, defined as a serum potassium value of 5.1 to < 6.5 mEq/L at screening Taking either an Angiotensin-Converting Enzyme (ACE) Inhibitor, an Angiotensin II receptor blocker (ARB), or an aldosterone antagonist (AA) medication Informed consent given Exclusion Criteria: Participants with auto-immune related chronic kidney disease such as lupus nephritis or renal scleroderma/scleroderma renal crisis, or mixed connective tissue disease with renal involvement Participants with uncontrolled Type 1 diabetes, defined as or a HbA1c > 10.0 %, or hospitalization to treat hyper- or hypo-glycemia in the past 3 months within the previous 6 months in participants with Type 2 diabetes Participants with severe heart failure, defined as NYHA (New York Heart Association) class IV Participants with major surgery including thoracic and cardiac, in the past 3 months, or participants with heart or kidney transplant Participants with significant cardiovascular or cerebrovascular events in the past 2 months, such as cardiac arrest, myocardial infarction, or stroke Participants with BMI ≥ 40 kg/m2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patiromer<br>Patiromer was administered twice a day as a powder mixed with water. | Drug: Patiromer<br> <br> * Other names: Veltassa;|
| Placebo Comparator: Placebo<br>Placebo was administered twice a day as a powder mixed with water. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Potassium From Part A Baseline to Part A Week 4 | The primary analysis endpoint is the change from Baseline at Week 4. The estimate of the change at Week 4 is from a repeated measures model, which includes data from Weeks 1, 2, 3 and 4. The analysis includes all intent to treat participants who had a serum potassium result at baseline and at least one weekly post-baseline visit (i.e. Part A Week 1 or later) and excludes six participants who had no result collected after Day 3). | Part A Baseline to Part A Week 4 | 
| Change in Serum Potassium From Part B Baseline | Change in Serum Potassium from Part B Baseline to either: Part B Week 4 visit, if the participant's serum potassium remained ≥ 3.8 mEq/L and < 5.5 mEq/L up to the Part B Week 4 visit or the earliest Part B visit at which the participant's serum potassium was < 3.8 mEq/L or ≥ 5.5 mEq/L. | Part B Baseline to Part B Week 4 or first local laboratory serum potassium < 3.8 mEq/L or ≥ 5.5 mEq/L | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Serum Potassium Levels in the Target Range of 3.8 to < 5.1 mEq/L at Part A Week 4 |  | Week 4 | 
| Proportion of Participants With Serum Potassium That Was ≥ 5.5 mEq/L in Part B |  | Part B Baseline to Part B Week 8 | 
| Proportion of Participants With Serum Potassium ≥ 5.1 mEq/L in Part B |  | Part B Baseline to Part B Week 8 | 

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