Chronic Kidney Disease, Hyperkalemia, Hypertension
Conditions
Keywords
Hyperkalemia, Chronic Kidney Disease, Treatment of Hyperkalemia, Hypertension, Diabetic Nephropathy
Brief summary
This study determined the optimal starting dose of patiromer in treating hyperkalemia in participants with hypertension and diabetic nephropathy who were already receiving ACEI and/or ARB drugs, with or without spironolactone. This study also evaluated the efficacy and safety of patiromer and the long term use of patiromer.
Detailed description
RLY5016-205 was an open-label, randomized, dose ranging study to determine the optimal starting dose, efficacy and safety of patiromer in treating hyperkalemia in hypertensive patients with nephropathy due to type 2 diabetes mellitus (T2DM) who were already receiving Angiotensin-converting Enzyme Inhibitor (ACEI) and/or Angiotensin II Receptor Blocker (ARB) drugs, with or without spironolactone. The study consisted of the following periods: * Screening: Up to 10 days (1 visit) * Run-in for those who were not hyperkalemic at screening (Cohorts 1 and 2): up to 4 weeks (1 to 4 visits) * Patiromer Treatment Initiation: first 8 weeks of patiromer treatment (a minimum of 10 visits) * Patiromer Long-Term Maintenance: additional 44 weeks of patiromer treatment up to a total of one year (minimum of 11 additional visits) * Follow-up (after patiromer discontinuation): 1 week (2 visits) OR 4 weeks (5 visits) depending on the final serum potassium level
Interventions
DRUGpatiromer
Cohorts 1, 2 and 3 - Patiromer starting dose: 8.4 g/day, orally, as a divided dose, twice daily. The dose of patiromer could be titrated based on participant's serum potassium response (Stratum 1)
DRUGlosartan
losartan dose: 100 mg/d, oral, once daily (initiated during Run-In Period; Cohort 1)
DRUGspironolactone
Spironolactone dose: 25 mg/d or up to 50 mg/d, oral, once daily (initiated during Run-In Period; Cohort 2)
Sponsors
Relypsa, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 30 - 80 years old at screening (S1) 2. Type 2 diabetes mellitus (T2DM) diagnosed after age 30 which has been treated with oral medications or insulin for at least 1 year prior to S1 3. Chronic kidney disease (CKD): estimated glomerular filtration rate (eGFR) 15 - \< 60 mL/min/1.73m2 at screening based on central lab serum creatinine measurement (except for participants with hyperkalemia at S1), whose eligibility will be assessed based on local lab eGFR value) 4. Urine albumin/creatinine ratio (ACR): 1. Cohorts 1 and 2: urine ACR ≥ 30 mg/g at S1 AND average urine ACR ≥ 30 mg/g at the beginning of Run-In Period (R0) based on up to three ACR values obtained starting at S1 and ending at the R0 Visit 2. Cohort 3: not applicable 5. Local laboratory serum potassium (K+) values of: 1. Cohorts 1 and 2: 4.3 - 5.0 mEq/L at S1; AND 4.5 - 5.0 mEq/L at R0; AND \> 5.0 - \< 6.0 mEq/L at randomization to patiromer (Baseline, T0 Visit) 2. Cohort 3: \> 5.0 - \< 6.0 mEq/L at S1 OR at R0 after same day confirmation 6. Must be receiving an ACEI and/or ARB for at least 28 days prior to screening 7. Average systolic blood pressure (SBP) ≥ 130 - \< 180 mmHg AND average DBP ≥ 80 - \< 110 mmHg (sitting) at both screening and R0 (as applicable) 8. 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 patiromer administration, during the study, and for one month after study completion 9. Provide their written informed consent prior to participation in the study
Exclusion criteria
1. Type 1 diabetes mellitus 2. Central lab hemoglobin A1c \> 12% at Screening 1 (S1) (except for Cohort 3 participants who are hyperkalemic at S1) 3. Emergency treatment for T2DM within the last 3 months 4. A confirmed SBP \> 180 mmHg or diastolic blood pressure (DBP) \> 110 mmHg at any time during SI or Run-In Period or at Baseline T0 Visit 5. Central lab serum magnesium \< 1.4 mg/dL (\< 0.58 mmol/L) at screening (Cohort 3 participants will be evaluated based on local lab serum magnesium measurement) 6. Central lab urine ACR ≥ 10000 mg/g at screening (except for Cohort 3 participants who are hyperkalemic at S1) 7. Confirmed diagnosis or history of renal artery stenosis (unilateral or bilateral) 8. Diabetic gastroparesis 9. Non-diabetic chronic kidney disease 10. History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery (e.g., large bowel resection) 11. Current diagnosis of NYHA (New York Heart Association) Class III or IV heart failure 12. Body mass index (BMI) ≥ 40 kg/m2 13. Any of the following events having occurred within 2 months prior to screening: unstable angina as judged by the Principal Investigator (PI), unresolved acute coronary syndrome, cardiac arrest or clinically significant ventricular arrhythmias, transient ischemic attack or stroke, use of any intravenous cardiac medication 14. Prior kidney transplant, or anticipated need for transplant during study participation 15. Active cancer, currently on cancer treatment or history of cancer in the past 2 years except for non-melanocytic skin cancer which is considered cured 16. History of alcoholism or drug/chemical abuse within 1 year 17. Central lab liver enzymes \[alanine aminotransferase (ALT), aspartate aminotransferase (AST)\] \> 3 times upper limit of normal at S1 (except for Cohort 3 patients with hyperkalemia at S1, who will have local lab ALT and AST) 18. Loop and thiazide diuretics or other antihypertensive medications (calcium channel blocker, beta-blocker, alpha-blocker, or centrally acting agent) that have not been stable for at least 28 days prior to screening or not anticipated to remain stable during study participation 19. Current use of polymer-based drugs (e.g., sevelamer, sodium polystyrene sulfonate, colesevelam, colestipol, cholestyramine), phosphate binders (e.g., lanthanum carbonate), or other potassium binders, or their anticipated need during study participation 20. Current use of lithium 21. Use of potassium sparing medications, including aldosterone antagonists (e.g., spironolactone), drospirenone, potassium supplements, bicarbonate or baking soda in the last 7 days prior to screening 22. Use of any investigational product within 30 days or 5 half-lives, whichever is longer, prior to screening 23. Inability to consume the investigational product, or, in the opinion of the Investigator, inability to comply with the protocol 24. In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, or serious intercurrent illness that would significantly decrease study compliance or jeopardize the safety of the participant or affect the validity of the trial results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group | Baseline to Week 4 or First Titration which could occur at any scheduled study visit after patiromer initiation. | Least square mean changes from Baseline to Week 4/first titration were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group | Baseline to Week 8 or First Titration which could occur at any scheduled study visit after patiromer initiation. | Least squares mean changes from Baseline to Week 8/first titration were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates. |
| Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group | Baseline to Day 3 | Least squares mean changes from Baseline to Day 3 were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates. |
| Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group | Baseline to Week 52 | — |
| Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group | Baseline to Week 8 | — |
| Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group | Baseline to Week 8 | — |
| Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group | Baseline to Week 8 | — |
| Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group | Baseline to Week 52 | — |
| Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days | Week 52 or Last Patiromer Dose (if Occurred before Week 52) to Following up Visit Plus 7 Days | — |
Countries
Croatia, Georgia, Hungary, Serbia, Slovenia
Participant flow
Recruitment details
324 participants were enrolled in the study; 306 participants were randomized to receive study drug.
Pre-assignment details
Screening serum potassium ≤ 5 mEq/L (milliequivalent) entered Run-in: Cohort 1 stopped ACEI/ARB (angiotensin-converting enzyme inhibitor/angiotensin receptor blockers), started losartan; Cohort 2 started spironolactone; Run-in (Cohorts 1 and 2) or screening (Cohort 3) \> 5 mEq/L entered study.
Participants by arm
| Arm | Count |
|---|---|
| Stratum 1: 8.4 g/d Patiromer Participants with baseline serum potassium \> 5.0 - 5.5 mEq/L randomized to 8.4 g/day patiromer starting dose, orally, as a divided dose twice a day. | 74 |
| Stratum 1: 16.8 g/d Patiromer Participants with baseline serum potassium \> 5.0 - 5.5 mEq/L randomized to 16.8 g/day patiromer starting dose, orally, as a divided dose twice a day. | 73 |
| Stratum 1: 25.2 g/d Patiromer Participants with baseline serum potassium \> 5.0 - 5.5 mEq/L randomized to 25.2 g/day patiromer starting dose, orally, as a divided dose twice a day. | 73 |
| Stratum 2: 16.8 g/d Patiromer Participants with baseline serum potassium \> 5.5 to \< 6.0 mEq/L randomized to 16.8 g/day patiromer starting dose, orally, as a divided dose twice a day. | 26 |
| Stratum 2: 25.2 g/d Patiromer Participants with baseline serum potassium \> 5.5 to \< 6.0 mEq/L randomized to 25.2 g/day patiromer starting dose, orally, as a divided dose twice a day | 28 |
| Stratum 2: 33.6 g/d Patiromer Participants with baseline serum potassium \> 5.5 to \< 6.0 mEq/L randomized to 33.6 g/day patiromer starting dose, orally, as a divided dose twice a day. | 30 |
| Total | 304 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Abnormal Renal Function | 0 | 2 | 0 | 1 | 0 | 1 |
| Overall Study | Adverse Event | 4 | 2 | 7 | 2 | 2 | 2 |
| Overall Study | Death | 1 | 0 | 4 | 1 | 2 | 0 |
| Overall Study | High Serum Potassium Results | 1 | 1 | 1 | 2 | 0 | 2 |
| Overall Study | Low Serum Potassium Results | 1 | 1 | 1 | 1 | 0 | 3 |
| Overall Study | Non-Compliance | 3 | 4 | 3 | 0 | 0 | 1 |
| Overall Study | Other Reasons | 2 | 1 | 2 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 12 | 5 | 2 | 2 | 4 |
Baseline characteristics
| Characteristic | Stratum 1: 16.8 g/d Patiromer | Stratum 1: 25.2 g/d Patiromer | Stratum 2: 16.8 g/d Patiromer | Stratum 2: 25.2 g/d Patiromer | Stratum 2: 33.6 g/d Patiromer | Stratum 1: 8.4 g/d Patiromer | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 44 Participants | 45 Participants | 14 Participants | 16 Participants | 17 Participants | 46 Participants | 182 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 28 Participants | 12 Participants | 12 Participants | 13 Participants | 28 Participants | 122 Participants |
| Age, Continuous | 70 years | 68 years | 66.5 years | 68.5 years | 65 years | 67 years | 67.5 years |
| Sex: Female, Male Female | 26 Participants | 26 Participants | 8 Participants | 13 Participants | 10 Participants | 29 Participants | 112 Participants |
| Sex: Female, Male Male | 47 Participants | 47 Participants | 18 Participants | 15 Participants | 20 Participants | 45 Participants | 192 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 74 | 29 / 73 | 29 / 73 | 14 / 26 | 14 / 28 | 22 / 30 |
| serious Total, serious adverse events | 9 / 74 | 10 / 73 | 10 / 73 | 6 / 26 | 5 / 28 | 4 / 30 |
Outcome results
Primary
Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group
Least square mean changes from Baseline to Week 4/first titration were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.
Time frame: Baseline to Week 4 or First Titration which could occur at any scheduled study visit after patiromer initiation.
Population: Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Stratum 1: 8.4 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group | -0.35 mEq/L | Standard Error 0.066 |
| Stratum 1: 16.8 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group | -0.51 mEq/L | Standard Error 0.067 |
| Stratum 1: 25.2 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group | -0.55 mEq/L | Standard Error 0.067 |
| Stratum 2: 16.8 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group | -0.87 mEq/L | Standard Error 0.134 |
| Stratum 2: 25.2 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group | -0.97 mEq/L | Standard Error 0.132 |
| Stratum 2: 33.6 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 4 or Time of First Titration for Each Individual Starting Dose Group | -0.92 mEq/L | Standard Error 0.125 |
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Secondary
Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group
Least squares mean changes from Baseline to Day 3 were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.
Time frame: Baseline to Day 3
Population: Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Stratum 1: 8.4 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group | -0.26 mEq/L | Standard Error 0.048 |
| Stratum 1: 16.8 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group | -0.28 mEq/L | Standard Error 0.05 |
| Stratum 1: 25.2 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group | -0.31 mEq/L | Standard Error 0.047 |
| Stratum 2: 16.8 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group | -0.65 mEq/L | Standard Error 0.086 |
| Stratum 2: 25.2 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group | -0.59 mEq/L | Standard Error 0.084 |
| Stratum 2: 33.6 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Day 3 During the Treatment Initiation Period for Each Individual Starting Dose Group | -0.53 mEq/L | Standard Error 0.079 |
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Secondary
Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group
Least squares mean changes from Baseline to Week 8/first titration were derived from parallel lines ANCOVA model with randomized starting dose and baseline serum potassium value as covariates.
Time frame: Baseline to Week 8 or First Titration which could occur at any scheduled study visit after patiromer initiation.
Population: Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Stratum 1: 8.4 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group | -0.35 mEq/L | Standard Error 0.07 |
| Stratum 1: 16.8 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group | -0.47 mEq/L | Standard Error 0.07 |
| Stratum 1: 25.2 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group | -0.54 mEq/L | Standard Error 0.07 |
| Stratum 2: 16.8 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group | -0.88 mEq/L | Standard Error 0.142 |
| Stratum 2: 25.2 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group | -0.95 mEq/L | Standard Error 0.139 |
| Stratum 2: 33.6 g/d Patiromer | Least Squares Mean Change in Serum Potassium From Baseline to Week 8 or Time of First Titration for Each Individual Starting Dose Group | -0.91 mEq/L | Standard Error 0.132 |
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Comparison: Each starting dose group was compared to its baseline.p-value: <0.001ANCOVA
Secondary
Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group
Time frame: Baseline to Week 52
Population: Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stratum 1: 8.4 g/d Patiromer | Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group | -0.54 mEq/L | Standard Deviation 0.465 |
| Stratum 1: 16.8 g/d Patiromer | Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group | -0.44 mEq/L | Standard Deviation 0.44 |
| Stratum 1: 25.2 g/d Patiromer | Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group | -0.50 mEq/L | Standard Deviation 0.417 |
| Stratum 2: 16.8 g/d Patiromer | Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group | -1.00 mEq/L | Standard Deviation 0.466 |
| Stratum 2: 25.2 g/d Patiromer | Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group | -0.96 mEq/L | Standard Deviation 0.414 |
| Stratum 2: 33.6 g/d Patiromer | Mean Change in Serum Potassium From Baseline to Week 52 During the Long-term Maintenance Period for Each Individual Starting Dose Group | -1.17 mEq/L | Standard Deviation 0.569 |
Comparison: Each starting dose group was compared to its baseline.
Comparison: Each starting dose group was compared to its baseline.
Comparison: Each starting dose group was compared to its baseline.
Comparison: Each starting dose group was compared to its baseline.
Comparison: Each starting dose group was compared to its baseline.
Comparison: Each starting dose group was compared to its baseline.
Secondary
Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days
Time frame: Week 52 or Last Patiromer Dose (if Occurred before Week 52) to Following up Visit Plus 7 Days
Population: Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stratum 1: 8.4 g/d Patiromer | Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days | 0.36 mEq/L | Standard Deviation 0.567 |
| Stratum 1: 16.8 g/d Patiromer | Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days | 0.22 mEq/L | Standard Deviation 0.424 |
| Stratum 1: 25.2 g/d Patiromer | Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days | 0.30 mEq/L | Standard Deviation 0.508 |
| Stratum 2: 16.8 g/d Patiromer | Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days | 0.41 mEq/L | Standard Deviation 0.66 |
| Stratum 2: 25.2 g/d Patiromer | Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days | 0.39 mEq/L | Standard Deviation 0.331 |
| Stratum 2: 33.6 g/d Patiromer | Mean Change in Serum Potassium From Week 52 or Last Patiromer Dose (if Occurred Before Week 52) to Follow-up Visits Plus 7 Days | 0.58 mEq/L | Standard Deviation 0.557 |
Comparison: Each starting dose group was compared to its baseline.
Comparison: Each starting dose group was compared to its baseline.
Comparison: Each starting dose group was compared to its baseline.
Comparison: Each starting dose group was compared to its baseline.
Comparison: Each starting dose group was compared to its baseline.
Comparison: Each starting dose group was compared to its baseline.
Secondary
Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group
Time frame: Baseline to Week 8
Population: Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum 1: 8.4 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group | 100 percentage of participants |
| Stratum 1: 16.8 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group | 100 percentage of participants |
| Stratum 1: 25.2 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group | 98.4 percentage of participants |
| Stratum 2: 16.8 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group | 91.7 percentage of participants |
| Stratum 2: 25.2 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group | 95.8 percentage of participants |
| Stratum 2: 33.6 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 3.5 to 5.5 mEq/L at Week 8 for Each Individual Starting Dose Group | 95.5 percentage of participants |
95% CI: [94.5, 100]
95% CI: [91.6, 100]
95% CI: [94.3, 100]
95% CI: [73, 99]
95% CI: [78.9, 99.9]
95% CI: [77.2, 99.9]
Secondary
Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group
Time frame: Baseline to Week 8
Population: Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum 1: 8.4 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group | 95.2 percentage of participants |
| Stratum 1: 16.8 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group | 90.8 percentage of participants |
| Stratum 1: 25.2 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group | 81.3 percentage of participants |
| Stratum 2: 16.8 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group | 79.2 percentage of participants |
| Stratum 2: 25.2 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group | 91.7 percentage of participants |
| Stratum 2: 33.6 g/d Patiromer | Proportion of Participants Achieving Serum Potassium Levels Within 4.0 to 5.0 mEq/L at Week 8 for Each Individual Starting Dose Group | 77.3 percentage of participants |
95% CI: [86.7, 99]
95% CI: [81, 96.5]
95% CI: [69.5, 89.9]
95% CI: [57.8, 92.9]
95% CI: [73, 99]
95% CI: [54.6, 92.2]
Secondary
Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group
Time frame: Baseline to Week 52
Population: Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum 1: 8.4 g/d Patiromer | Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group | 86.3 percentage of participants |
| Stratum 1: 16.8 g/d Patiromer | Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group | 81.6 percentage of participants |
| Stratum 1: 25.2 g/d Patiromer | Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group | 88.9 percentage of participants |
| Stratum 2: 16.8 g/d Patiromer | Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group | 86.7 percentage of participants |
| Stratum 2: 25.2 g/d Patiromer | Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group | 89.5 percentage of participants |
| Stratum 2: 33.6 g/d Patiromer | Proportions of Participants Achieving Serum Potassium Levels Within 3.8 to 5.0 mEq/L at Week 52 for Each Individual Starting Dose Group | 93.3 percentage of participants |
95% CI: [73.7, 94.3]
95% CI: [68, 91.2]
95% CI: [75.9, 96.3]
95% CI: [59.5, 98.3]
95% CI: [66.9, 98.7]
95% CI: [68.1, 99.8]
Secondary
Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group
Time frame: Baseline to Week 8
Population: Included all randomized participants who received at least 1 dose of patiromer. Analyses of endpoints included participants with available central laboratory potassium values at the time point of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1: 8.4 g/d Patiromer | Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group | 4 Days |
| Stratum 1: 16.8 g/d Patiromer | Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group | 4 Days |
| Stratum 1: 25.2 g/d Patiromer | Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group | 4 Days |
| Stratum 2: 16.8 g/d Patiromer | Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group | 8 Days |
| Stratum 2: 25.2 g/d Patiromer | Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group | 7.5 Days |
| Stratum 2: 33.6 g/d Patiromer | Time to First Serum Potassium Measurement of 4.0 - 5.0 mEq/L During Treatment Initiation Period for Each Individual Starting Dose Group | 8 Days |