Exploratory Study of ZG-801 for the Treatment of Hyperkalemia

Study Overview
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Brief Summary
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To investigate the efficacy of each ZG-801 starting dose and the titration algorithm of ZG-801 for the treatment of hyperkalemia in Japanese patients. To evaluate the safety of ZG-801 for the chronic use (total over 52 weeks). In addition, to confirm the safety after the discontinuation of ZG-801 treatment on 1 week follow-up.

Official Title
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ZG-801 Phase II Trial - Exploratory Study of Efficacy and Safety on Patients With Hyperkalemia, and Long Term Safety Study -

Conditions
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Hyperkalemia

Intervention / Treatment
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* Drug: patiromer
* Drug: patiromer
* Drug: placebo
* Drug: placebo
* Drug: patiromer
* Drug: patiromer
* Drug: patiromer
* Drug: patiromer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ages 18 - 80 Informed consent given Serum Potassium measurement at baseline is 5.1 to < 6.5 mEq/L (Non-dialysis patients or 5.5 to < 6.5 mEq/L (Dialysis patients) Exclusion Criteria: Subjects with hospitalization for hyper- or hypoglycemia with Type 2 diabetes or for acute exacerbations of heart failure within the previous 3 months Subjects with severe heart failure, defined as NYHA (New York Heart Association) class IV Subjects with uncorrected hemodynamically significant primary vascular disease or uncontrolled or hemodynamically unstable arrhythmia Subjects with coronary artery bypass graft, percutaneous intervention, or major surgery including thoracic and cardiac, within the previous 3 months or anticipated need during study participation Subjects with heart, liver (only Dialysis patients), or kidney transplant recipient, or anticipated need for transplant during the study period Subjects with any of the significant cardiovascular or cerebrovascular events within the previous 2 months Subjects with a history of or current diagnosis of a severe swallowing disorder, moderate to severe gastroparesis, or history of bariatric surgery, bowel obstruction or severe gastrointestinal disorders or major gastrointestinal surgery Subjects who cannot use the oral concomitant medication to be separate 3 hours from ZG-801 medication Subjects suspected of transient high potassium levels, such as those caused only by dietary effects

Ages Eligible for Study
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Minimum Age: 20 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stratum 1: 8.4 g patiromer<br>Non-dialysis subjects with serum potassium 5.1 to < 6.0 mEq/L range at baseline | Drug: patiromer<br>* Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1)<br>|
| Experimental: Stratum 1: 16.8 g patiromer<br>Non-dialysis subjects with serum potassium 5.1 to < 6.0 mEq/L range at baseline | Drug: patiromer<br>* Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1)<br>|
| Experimental: Stratum 1: placebo of 8.4 g patiromer<br>Non-dialysis subjects with serum potassium 5.1 to < 6.0 mEq/L range at baseline | Drug: placebo<br>* Placebo starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1)<br>|
| Experimental: Stratum 1: placebo of 16.8 g patiromer<br>Non-dialysis subjects with serum potassium 5.1 to < 6.0 mEq/L range at baseline | Drug: placebo<br>* Placebo starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 1)<br>|
| Experimental: Stratum 2: 8.4 g patiromer<br>Non-dialysis subjects with serum potassium 6.0 to < 6.5 mEq/L range at baseline | Drug: patiromer<br>* Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2)<br>|
| Experimental: Stratum 2: 16.8 g patiromer<br>Non-dialysis subjects with serum potassium 6.0 to < 6.5 mEq/L range at baseline | Drug: patiromer<br>* Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 2)<br>|
| Experimental: Stratum 3: 8.4 g patiromer<br>Dialysis subjects with serum potassium 5.5 to < 6.5 mEq/L range at baseline | Drug: patiromer<br>* Patiromer starting dose: 1 packet/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3)<br>|
| Experimental: Stratum 3: 16.8 g patiromer<br>Dialysis subjects with serum potassium 5.5 to < 6.5 mEq/L range at baseline | Drug: patiromer<br>* Patiromer starting dose: 2 packets/day, orally, once daily. The dose of patiromer could be titrated based on subject's serum potassium response (stratum 3)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum potassium from baseline to 1 week after the start of administration in each group of starting dose |  | Baseline to week 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum potassium 4 weeks after the start of administration in each group of starting dose |  | Baseline to week 4 | 
| Proportion of subjects with a normalized serum potassium level at 4 weeks after the start of administration in each group of starting dose |  | Week 4 | 
| Incidence of adverse events |  | Over 52-week study period | 
| Incidence of adverse drug reactions |  | Over 52-week study period |