A Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ZS) Among Patients With S-K ≥5.8

Study Overview
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Brief Summary
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The study is designed to determine if ZS 10g administered up to three times over 10h added to insulin and glucose in patients presenting with hyperkalemia will prove tolerable and efficacious. Patients will receive ZS or Placebo on top of standard of care treatment with insulin and glucose.

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate a Potassium Normalization Treatment Regimen Including Sodium Zirconium Cyclosilicate (ENERGIZE)

Conditions
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Hyperkalemia

Intervention / Treatment
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* Drug: Placebo
* Drug: Sodium Zirconium Cyclosilicate(ZS)
* Drug: Insulin
* Drug: Glucose
* Drug: Insulin
* Drug: Glucose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age Potassium ≥5.8 mmol/L Exclusion Criteria: Possible pseudohyperkalaemia Hyperkalaemia caused by any condition for which a therapy directed against the underlying cause of hyperkalaemia would be a better treatment option than treatment with insulin and glucose. Dialysis session expected within 4h after randomization Treated with any therapy intended to lower S-K between arriving at the hospital and randomization during Visit 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZS+insulin+glucose<br>ZS will be administered in addition to insulin and glucose. Insulin and glucose is the current standard of care to treat serum potassium ≥5.8mmol/L. | Drug: Sodium Zirconium Cyclosilicate(ZS)<br>* Suspension administered orally for a treatment period of 24h. Single dose contains 2 sachets of ZS 5g. 10g administered up to three times over 10h (at 0, 4 and 10h).<br>* Other names: ZS, ZS-9;Drug: Insulin<br>* Insulin 0.1 units/kg administered as a bolus or for up to 30 minutes.<br>Drug: Glucose<br>* Glucose 25g administered IV <15 minutes before the insulin.<br>|
| Placebo Comparator: Placebo+insulin+glucose<br>Placebo will be administered in addition to insulin and glucose. Insulin and glucose is the current standard of care to treat serum potassium ≥5.8mmol/L. | Drug: Placebo<br>* Suspension administered orally for a treatment period of 24h. 2 sachets administered up to three times over 10h (at 0, 4 and 10h).<br>Drug: Insulin<br>* Insulin 0.1 units/kg administered as a bolus or for up to 30 minutes.<br>Drug: Glucose<br>* Glucose 25g administered IV <15 minutes before the insulin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Absolute Change in S-K From Baseline Until 4h After Start of Dosing With SZC/Placebo | The least squares means (LS-means) are derived from a linear regression model of absolute change in S-K at 4h with the following covariates: treatment group; baseline S-K; time from the start of dosing insulin to the start of dosing SZC/placebo and the dose (units/kg) of the first course of insulin. The 95% CI is associated with LS-Means. | Baseline to 4h potassium measurements. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fraction of Patients Responding to Therapy Defined as: S-K <6.0mmol/L Between 1 and 4h and S-K <5.0mmol/L at 4h; and no Additional Potassium Lowering Therapy From 0 to 4h With Exception of the Initial Insulin Treatment | Additional therapies for hyperkalaemia are 2nd dose of insulin, Beta-agonists, Diuretics, Dialysis, Sodium bicarbonate and Potassium binders when administered with the expressed intent to lower S-K. Patients with any missing potassium value from 1h to 4h inclusive will be treated as non-responders. | Baseline to 4h potassium meansurements. | 
| The Fraction of Patients Achieving Normokalaemia 1, 2 and 4h After Start of Dosing With SZC/Placebo | Proportion of patients achieving normokalaemia, S-K 3.5-5.0 mmol/L, at 1, 2 and 4h after start of dosing | Baseline to 4h potassium meansurements. | 
| The Fraction of Patients Achieving S-K <5.5mmol/l 1, 2, and 4h After Start of Dosing With SZC/Placebo |  | Baseline to 4h potassium meansurements. | 
| The Fraction of Patients Achieving S-K <6.0mmol/l 1, 2, and 4h After Start of Dosing With SZC/Placebo |  | Baseline to 4h potassium meansurements. | 
| The Fraction of Patients Administered Additional Potassium Lowering Therapy Due to Hyperkalaemia From 0 to 4h. | Additional therapies for hyperkalaemia are 2nd dose of insulin, Beta-agonists, Diuretics, Dialysis, Sodium bicarbonate and Potassium binders when administered with the expressed intent to lower S-K. | Baseline to 4h potassium meansurements. | 
| Mean Absolute Change in S-K From Baseline to 1h and 2h After Start of Dosing With SZC/Placebo | The least squares means (LS-means) are derived from a linear regression model of absolute change in S-K at 1h and 2h with the following covariates: treatment group; baseline S-K; time from the start of dosing insulin to the start of dosing SZC/placebo and the dose (units/kg) of the first course of insulin. The 95% CI is associated with LS-Means. | Baseline to 2h potassium measurements. |