Evaluation of Patiromer in Heart Failure Patients

Study Overview
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Brief Summary
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The purpose of this study was to assess the effects of patiromer on serum potassium participants with heart failure. This study also assessed the safety and tolerability of patiromer in participants with heart failure.

Detailed Description
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This was a double-blind, randomized, placebo-controlled, parallel-group, multiple-dose study in congestive heart failure participants. Depending on the outcome from the initial cohort of 100 participants (Part 1), a second cohort of 170 participants could have been enrolled (Part 2). Based on the results of Part 1 of the study, Part 2 was not conducted. Participants were randomly assigned to and received patiromer (30 g/day) or placebo for up to 28 days. All participants also received spironolactone; the initial spironolactone dose was 25 mg daily and was increased to 50 mg daily for participants who had a serum potassium ≤ 5.1 mEq/L on treatment Day 14. Study visits occurred on treatment Days 3, 7, 14, 17, 21 and 28. A safety follow-up contact was made 7 days after administration of last dose of study drug.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Multiple-Dose Study to Evaluate the Effects of Patiromer in Heart Failure Patients

Conditions
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Hyperkalemia, Heart Failure

Intervention / Treatment
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* Drug: patiromer
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with chronic heart failure clinically indicated to receive spironolactone therapy, aged 18 years or older with serum potassium level of 4.3 - 5.1 mEq/L at screening and baseline, AND (1) chronic kidney disease (GFR < 60 mL/min) OR (2) documented history of hyperkalemia within the last 6 months Females of child-bearing potential must be non-lactating, must have a negative serum pregnancy test at screening, and must have used a highly effective form of contraception for at least 3 months before study drug administration, during the study, and for one month after study completion Male participants and/or their female partners of child-bearing potential must use a highly effective form of contraception during the study and for 3 months after study completion Must sign informed consent document Exclusion Criteria: History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery Uncorrected hemodynamically significant primary valvular disease, known obstructive or restrictive cardiomyopathy, uncontrolled or hemodynamically unstable arrhythmia Coronary-artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, aortic), or major surgery including thoracic and cardiac, within 3 months prior to baseline or anticipated need during study participation Heart transplant recipient, or anticipated need for transplant during study participation Any of the following events having occurred within 3 months prior to baseline: unstable angina as judged by the Investigator, unresolved acute coronary syndrome, transient ischemic attack or stroke Current dialysis participant, or anticipated need for dialysis during study participation Prior kidney transplant, or anticipated need for transplant during study participation Metastatic, late-stage or end-stage cancer with < 12 months life expectancy History of alcoholism or drug/chemical abuse within 1 year QTcB interval > 500 msec (Bazett's correction formula) Sustained systolic blood pressure > 170 or < 90 mmHg Liver enzymes (ALT, AST) > 3 times upper limit of normal Use of oral cardiac medications (including loop and thiazide diuretics) that have not been stable for at least 21 days prior to baseline and are not anticipated to remain stable during study participation Use of any IV cardiac medications within 21 days prior to baseline, or their anticipated need during study participation. Current use of polymer-based drugs (e.g. Renagel, Kayexalate, Welchol, Colestid), other phosphate binders or potassium binders, calcium supplements, antacids (eg TUMS, Maalox), or their anticipated need during study participation Use of aldosterone antagonist in the last 30 days prior to baseline, unless was discontinued due to hyperkalemia Use of potassium sparing medication and/or potassium supplements in the last 30 days prior to baseline Use of any investigational medication, 30 days or 5 half-lives whichever is longer, prior to baseline Participants who have taken investigational product in this study, or a previous patiromer study Inability to consume the study medication, or, in the opinion of the Investigator, inability to comply with the protocol In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, serious intercurrent illness, or extenuating circumstance occurring or persisting, within 30 days prior to baseline, that would significantly decrease study compliance or jeopardize the safety of the participant or affect the validity of the trial results

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: patiromer<br> | Drug: patiromer<br>* Active investigational drug<br>* Other names: Veltassa;|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Serum Potassium to the End of the 28-day Treatment Period. |  | Baseline and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With a Serum Potassium Level During the 28-day Treatment Period That Was > 5.5 mEq/L. | Analysis based on central laboratory data. | 28 Days | 
| Proportion of Participants Discontinuing the Study Due to Serum Potassium Elevation (Serum K+ > 5.5 mEq/L). | Analysis based on local laboratory data. | 28 Days | 
| Proportion of Participants Whose Spironolactone Dose Was Increased. |  | 28 Days | 
| Proportion of Participants With an Increase in Serum Potassium Level From Baseline to the End of the 28-day Treatment Period That Was ≥ 0.5 mEq/L |  | Baseline and Day 28 | 
| Time to First Elevated Serum K+ > 5.5 mEq/L. |  | 28 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HF, Heart failure, hyperkalemia, chronic kidney disease, prevention of hyperkalemia in heart failure participants