Chronic Kidney Disease, Hyperkalaemia, Metabolic Acidosis
Conditions
Brief summary
The main objective of this study is to evaluate the efficacy of SZC as compared to placebo in maintaining normal sK+ in patients with hyperkalemia and metabolic acidosis associated with CKD
Detailed description
NEUTRALIZE is a prospective, randomized, double-blind, placebo-controlled, parallel, multicenter, Phase IIIb study to investigate the safety and efficacy of SZC in patients with hyperkalemia and low bicarbonate (metabolic acidosis ). The study will be conducted in the United States (US) at approximately 35 investigative sites. After screening on Day 1, all eligible patients will receive open-label SZC for up to 48 hours. Patients who achieve normokalemia within 48 hours will be randomized 1:1 into the double-blind randomized treatment phase to receive SZC or placebo. Study treatment will end with the Day 29 visit, which will be followed by a follow-up visit 7 days after the last administration of study medication.
Interventions
Investigational medicinal product
DRUGPlacebo
Plabeco comparator
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
NEUTRALIZE is a prospective, randomized, double-blind, placebo-controlled, parallel, multicenter, Phase IIIb study
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged ≥18 years * Participants who have CKD stage 3-5, not on dialysis. * POCT K+ level \>5 mmol/L to ≤5.9 mmol/L and POCT bicarbonate levels between 16-20 mmol/L inclusive prior to the first SZC dose on study Day 1 * Ability to have repeated blood draws or effective venous catheterization. * Male and/or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Capable of giving signed informed consent
Exclusion criteria
* Participants with pseudohyperkalemia. * Dialysis requirement or anticipated by the investigator to require dialysis therapy within 1 month, history of renal transplant, or life expectancy less than 3 months. * Cardiac arrhythmias requiring immediate treatment. * Active or suspected diabetic ketoacidosis. * POCT bicarbonate low enough to need emergency intervention or treatment as judged by the investigator. * Acute/chronic worsening renal function (eg, ≥30% decline in eGFR) in the 3 months before screening. * Current acute decompensated HF, hospitalization due to decompensated HF within 4 weeks prior to screening, or myocardial infarction (MI), unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to screening. * Coronary revascularization (percutaneous coronary intervention \[PCI\] or coronary artery bypass grafting \[CABG\]) or valvular repair/replacement within 12 weeks prior to screening or planned to undergo any of these operations. * Symptomatic hypotension. * Current exacerbation of chronic obstructive pulmonary disease (COPD)/asthma or hospitalization due to exacerbation of COPD/asthma within 4 weeks of screening. * Severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders * Active malignancy requiring treatment. * History of QT prolongation associated with other medications that required discontinuation of that medication. * Congenital long QT syndrome. * Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication are permitted. * QTcF (QT interval corrected by the Fridericia method) \>550 msec. * Active treatment (within 7 days prior to screening) with SZC, sodium bicarbonate, sodium polystyrene sulfonate, lactulose, or patiromer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase | Day 1 of randomization phase to Day 29 | Response was defined as a subject having serum potassium (sK+) within 3.5-5.0 mmol/L at the EOT visit, and no use of rescue therapy for hyperkalaemia at any point during the randomized placebo-controlled period. Participants who used rescue therapy for hyperkalaemia at any point during the randomized placebo-controlled period were assigned a non-response. Participants who died prior to the EOT visit were treated as non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | Day 1 to Day 29 of randomization phase | Occurrence (yes/no) of participants having an increase in serum bicarbonate of greater than or equal to 3 mmol/L from baseline (Day 1) to EOT (Day 29) without need for rescue treatment for metabolic acidosis (low bicarbonate). Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 3 mmol/L at the EOT visit without the need for rescue therapy for low bicarbonate. Participants who used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response. |
| Occurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L | Day 1 to Day 29 of randomization phase | Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 22 mmol/L at the EOT visit without the need for rescue therapy for low bicarbonate. Participants who had used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who died prior to the EOT visit were assigned a non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. |
| Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | Day 1 to Day 29 of randomization phase | Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 2 mmol/L at the EOT visit and no use of rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period. Participants who used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response. |
| Mean Serum Bicarbonate at Day 29 | Day 29 | Least-squares mean calculated with a repeated measures analysis of covariance model where the dependent variable was post randomization serum bicarbonate and with fixed terms for randomized treatment group and serum bicarbonate. |
| Occurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate) | Day 1 to Day 29 of randomization phase | Response was defined as a participant with sK+ within 3.5-5.0 mmol/L and serum bicarbonate greater than or equal to 22 mmol/L at the EOT visit without the need for rescue therapy for hyperkalaemia or low bicarbonate. Participants who used rescue therapy for hyperkalaemia or low bicarbonate at any point during the randomized placebo-controlled period were assigned a non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response. |
| Occurrence (Yes/no) of Participants Needing Rescue Treatment for Low Sodium Bicarbonate | Day 1 to Day 29 of randomization phase | Occurrence (yes/no) of participants needing rescue treatment for low sodium bicarbonate any time during the randomized phase |
| Participants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia | Day 1 to Day 29 of randomization phase | Participants with normal sK+ between 3.5 and 5.0 mmol/L inclusive at EOT and increase in serum bicarbonate greater than or equal to 3 mmol/L from Day 1 without rescue treatment for metabolic acidosis (low bicarbonate) or hyperkalemia. Response was a participant with sK+ within 3.5-5.0 mmol/L and increase in serum bicarbonate greater than or equal to 3 mmol/L at the EOT visit and no use of rescue therapy for hyperkalaemia or low bicarbonate at any point during the randomized placebo-controlled period. Participants who used rescue therapy for low bicarbonate or HK during the randomized placebo-controlled period had last observation prior to rescue therapy carried forward. Participants lost to follow-up prior to EOT visit had response as missing. Logistic regression model included response status (response/non-response) as dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response. |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
One participants was randomized to the double-blind treatment phase in error but did not receive treatment. This participant is noted as not completing the open-label phase in the table below.
Participants by arm
| Arm | Count |
|---|---|
| Sodium Zirconium Cyclosilicate (SZC) Open label phase: Three times daily (TID) 10 g SZC for up to 48 hours. Participants not achieving normokalemia or normokalemic at Day 2 continued in the open-label correction phase at 10 g SZC TID for an additional 24 hours and repeat point of care test on the next day (Day 3).
Double-blind treatment phase: Double-blind TID 10 g SZC for up to 48 hours | 17 |
| Placebo Open label phase: Three times daily (TID) 10 g SZC for up to 48 hours. Participants not achieving normokalemia or normokalemic at Day 2 continued in the open-label correction phase at 10 g SZC TID for an additional 24 hours and repeat point of care test on the next day (Day 3).
Double-blind treatment phase: Double-blind placebo for up to 48 hours | 20 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Treatment Phase | Adverse Event | 0 | 1 |
| Double-blind Treatment Phase | Death | 0 | 1 |
| Double-blind Treatment Phase | Investigator decision to start rescue therapy for hyperkalemia | 0 | 1 |
| Double-blind Treatment Phase | Missed doses whilst in hospital | 0 | 1 |
| Double-blind Treatment Phase | Physician Decision | 0 | 1 |
| Double-blind Treatment Phase | Withdrawal by Subject | 1 | 0 |
| Open-label Period | Did not meet randomization criteria for double-blind treatment phase | 1 | 0 |
| Open-label Period | Randomized who did not receive treatment | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Sodium Zirconium Cyclosilicate (SZC) |
|---|---|---|---|
| Age, Continuous | 65.9 years STANDARD_DEVIATION 11.13 | 63.3 years STANDARD_DEVIATION 14.09 | 60.3 years STANDARD_DEVIATION 16.77 |
| Age, Customized 18-64 | 9 Participants | 18 Participants | 9 Participants |
| Age, Customized 65-84 | 11 Participants | 19 Participants | 8 Participants |
| Age, Customized >=85 | 0 Participants | 0 Participants | 0 Participants |
| Chronic Heart Failure Status No | 20 Participants | 37 Participants | 17 Participants |
| Chronic Heart Failure Status Yes | 0 Participants | 0 Participants | 0 Participants |
| Chronic Kidney Disease (CKD) Status Missing | 3 Participants | 4 Participants | 1 Participants |
| Chronic Kidney Disease (CKD) Status Stage 3 | 3 Participants | 4 Participants | 1 Participants |
| Chronic Kidney Disease (CKD) Status Stage 4 | 8 Participants | 22 Participants | 14 Participants |
| Chronic Kidney Disease (CKD) Status Stage 5 | 6 Participants | 7 Participants | 1 Participants |
| Diabetes status No | 5 Participants | 11 Participants | 6 Participants |
| Diabetes status Yes | 15 Participants | 26 Participants | 11 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants | 10 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 16 Participants | 27 Participants | 11 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 18 Participants | 32 Participants | 14 Participants |
| Sex: Female, Male Female | 8 Participants | 12 Participants | 4 Participants |
| Sex: Female, Male Male | 12 Participants | 25 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 17 | 1 / 20 |
| other Total, other adverse events | 1 / 38 | 4 / 17 | 9 / 20 |
| serious Total, serious adverse events | 0 / 38 | 1 / 17 | 2 / 20 |
Outcome results
Primary
Occurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase
Response was defined as a subject having serum potassium (sK+) within 3.5-5.0 mmol/L at the EOT visit, and no use of rescue therapy for hyperkalaemia at any point during the randomized placebo-controlled period. Participants who used rescue therapy for hyperkalaemia at any point during the randomized placebo-controlled period were assigned a non-response. Participants who died prior to the EOT visit were treated as non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing.
Time frame: Day 1 of randomization phase to Day 29
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase | No response | 1 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase | Response | 15 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase | Missing | 1 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase | Response | 4 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase | Missing | 1 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase | No response | 15 Participants |
p-value: 0.00195% CI: [5.6, 563.6]Wald Chi-Squared test
Secondary
Mean Serum Bicarbonate at Day 29
Least-squares mean calculated with a repeated measures analysis of covariance model where the dependent variable was post randomization serum bicarbonate and with fixed terms for randomized treatment group and serum bicarbonate.
Time frame: Day 29
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (SZC) | Mean Serum Bicarbonate at Day 29 | 18.17 mmol/L | Standard Error 0.58 |
| Placebo | Mean Serum Bicarbonate at Day 29 | 16.52 mmol/L | Standard Error 0.56 |
Comparison: Difference between groupsp-value: 0.0595% CI: [0, 3.29]t-test, 2 sided
Secondary
Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate)
Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 2 mmol/L at the EOT visit and no use of rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period. Participants who used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.
Time frame: Day 1 to Day 29 of randomization phase
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | No response | 8 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | Response | 8 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | Missing | 1 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | No response | 13 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | Missing | 1 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | Response | 6 Participants |
Comparison: Comparison between groupsp-value: 0.27195% CI: [0.5, 8.6]Wald Chi-Squared test
Secondary
Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate)
Occurrence (yes/no) of participants having an increase in serum bicarbonate of greater than or equal to 3 mmol/L from baseline (Day 1) to EOT (Day 29) without need for rescue treatment for metabolic acidosis (low bicarbonate). Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 3 mmol/L at the EOT visit without the need for rescue therapy for low bicarbonate. Participants who used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.
Time frame: Day 1 to Day 29 of randomization phase
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | No response | 10 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | Response | 6 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | Missing | 1 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | No response | 16 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | Response | 3 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) | Missing | 1 Participants |
Comparison: Comparison between groupsp-value: 0.15395% CI: [0.6, 15.8]Wald Chi-Squared test
Secondary
Occurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L
Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 22 mmol/L at the EOT visit without the need for rescue therapy for low bicarbonate. Participants who had used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who died prior to the EOT visit were assigned a non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor.
Time frame: Day 1 to Day 29 of randomization phase
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L | No response | 14 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L | Response | 2 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L | Missing | 1 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L | No response | 19 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L | Response | 0 Participants |
| Placebo | Occurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L | Missing | 1 Participants |
Comparison: Comparison between groupsp-value: 0.94Wald Chi-Squared test
Secondary
Occurrence (Yes/no) of Participants Needing Rescue Treatment for Low Sodium Bicarbonate
Occurrence (yes/no) of participants needing rescue treatment for low sodium bicarbonate any time during the randomized phase
Time frame: Day 1 to Day 29 of randomization phase
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Needing Rescue Treatment for Low Sodium Bicarbonate | Rescue treatment required | 0 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Participants Needing Rescue Treatment for Low Sodium Bicarbonate | Rescue treatment not required | 17 Participants |
| Placebo | Occurrence (Yes/no) of Participants Needing Rescue Treatment for Low Sodium Bicarbonate | Rescue treatment required | 0 Participants |
| Placebo | Occurrence (Yes/no) of Participants Needing Rescue Treatment for Low Sodium Bicarbonate | Rescue treatment not required | 20 Participants |
Secondary
Occurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate)
Response was defined as a participant with sK+ within 3.5-5.0 mmol/L and serum bicarbonate greater than or equal to 22 mmol/L at the EOT visit without the need for rescue therapy for hyperkalaemia or low bicarbonate. Participants who used rescue therapy for hyperkalaemia or low bicarbonate at any point during the randomized placebo-controlled period were assigned a non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.
Time frame: Day 1 to Day 29 of randomization phase
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate) | No response | 14 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate) | Response | 2 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Occurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate) | Missing | 1 Participants |
| Placebo | Occurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate) | No response | 19 Participants |
| Placebo | Occurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate) | Response | 0 Participants |
| Placebo | Occurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate) | Missing | 1 Participants |
Comparison: Comparison between groupsp-value: 0.94Wald Chi-Squared test
Secondary
Participants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia
Participants with normal sK+ between 3.5 and 5.0 mmol/L inclusive at EOT and increase in serum bicarbonate greater than or equal to 3 mmol/L from Day 1 without rescue treatment for metabolic acidosis (low bicarbonate) or hyperkalemia. Response was a participant with sK+ within 3.5-5.0 mmol/L and increase in serum bicarbonate greater than or equal to 3 mmol/L at the EOT visit and no use of rescue therapy for hyperkalaemia or low bicarbonate at any point during the randomized placebo-controlled period. Participants who used rescue therapy for low bicarbonate or HK during the randomized placebo-controlled period had last observation prior to rescue therapy carried forward. Participants lost to follow-up prior to EOT visit had response as missing. Logistic regression model included response status (response/non-response) as dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.
Time frame: Day 1 to Day 29 of randomization phase
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (SZC) | Participants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia | No response | 10 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Participants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia | Response | 6 Participants |
| Sodium Zirconium Cyclosilicate (SZC) | Participants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia | Missing | 1 Participants |
| Placebo | Participants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia | No response | 18 Participants |
| Placebo | Participants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia | Response | 1 Participants |
| Placebo | Participants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia | Missing | 1 Participants |
Comparison: Comparison between groupsp-value: 0.03995% CI: [1.1, 102.8]Wald Chi-Squared test