E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hyperkalemia requiring urgent therapy (serum potassium more than or equal to 5.8mmol/L). |
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E.1.1.1 | Medical condition in easily understood language |
High level of potassium in blood. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020646 |
E.1.2 | Term | Hyperkalaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of ZS vs placebo when added to insulin and glucose on the reduction of potassium at 4 hours after start of dosing |
|
E.2.2 | Secondary objectives of the trial |
- To assess the effect of ZS vs placebo when added to insulin and glucose on the response to therapy
- To assess the effect of ZS vs placebo when added to insulin and glucose on the change in
serum potassium at 1h and 2h after start of dosing
- To assess the effect of ZS vs placebo when added to insulin and glucose on achieving normokalaemia
-To assess the effect of ZS vs placebo when added to insulin and glucose on achieving S-K <5.5mmol/l and <6.0mmol/l
-To assess the need for additional therapies for hyperkalaemia between ZS and placebo when added to insulin and glucose
Safety Objectives:
-To characterize the safety of ZS when added to insulin and glucose |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• ≥ 18 years of age at the time of signing the informed consent form.
• S-K ≥ 5.8 mmol/L, as determined using an i-STAT device. Patients with S-K 5.8 or 5.9 mmol/L can be included only if treatment of the patient with insulin and glucose is in accordance with the local standard of care. S-K measured by local laboratory prior to insulin administration may replace S-K measured by i-STAT for assessment against this inclusion criterion for patients having received insulin before signing the informed consent form. |
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E.4 | Principal exclusion criteria |
• Possible pseudohyperkalaemia as assessed by the investigator, e.g. secondary to hemolyzed blood specimen.
• 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. This includes, but is not limited to hyperkalaemia reasonably likely to be caused by physical injury, intoxication, pre-renal kidney failure, substance abuse, diabetic ketoacidosis and rhabdomyolysis.
• Presence of any other acute or chronic medical condition which, in the opinion of the investigator, places the patient at undue risk due to the severity of illness or potentially jeopardizes patients' ability to follow study procedures in the acute setting. Patients having any acute or chronic medical condition other than hyperkalaemia that would alone require immediate treatment in the hospital setting at Visit 1. are not eligible for the study.
• 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. with exception of patients meeting the following criteria:
- Treated with no more than one course of insulin since arriving at the hospital.
- S-K measured by i-STAT device or local laboratory prior to administration of insulin. S-K must have met Inclusion criterion 4.
- Reasonably likely to randomize, have screening and 0h assessments done, and dose the patient with ZS/placebo within 30 minutes of the start of administration of insulin. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean absolute change in S-K from baseline until 4h after start of dosing with ZS/placebo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
start of dosing untill 4h |
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E.5.2 | Secondary end point(s) |
1. Fraction of patients responding to therapy with responders to therapy defined as
• S-K <6.0mmol/L between 1 and 4h and S-K <5.0mmol/L at 4h
AND
• No additional therapy administered for hyperkalaemia from 0 to 4h with exception of the initial insulin treatment administered
2.Mean absolute change in S-K from baseline to 1h and 2h after start of dosing with ZS/placebo
3. The fraction of patients achieving normokalaemia 1, 2 and 4h after start of dosing ZS/placebo
4. The fraction of patients achieving S-K <5.5mmol/l and <6.0mmol/l 1, 2, and 4h after start of dosing ZS/placebo
5.The fraction of patients administered additional potassium lowering therapy due to hyperkalaemia from 0 to 4h. The considered therapies are:
• 2nd dose of insulin
• Beta-agonists
• Diuretics
• Dialysis
• Sodium bicarbonate
• Potassium binders
6.Safety Endpoint:
Adverse events (AEs) and serious AEs (SAEs)
Changes in vital signs (VS), physical examinations, and ECGs
Changes in clinical laboratory parameters, including assessment of hypokalaemia using S-K
measurements and of hypoglycaemia using P-glucose measurements |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. between 0h and 4h, at 4h
2. from baseline to 1h and 2h after starting the dose
3.1h, 2h and 4h after start of dosing;
4.1h, 2h, and 4h after start of dosing;
5. from 0 to 4h
6. from baseline untill study completion |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Denmark |
Italy |
Russian Federation |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of the Last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |