Chronic Kidney Disease (CKD), Hyperkalemia (HK)
Conditions
Keywords
Chronic Kidney Disease, Treatment of Hyperkalemia, Hyperkalemia
Brief summary
The purpose of this study was to evaluate the efficacy and safety of patiromer (investigational drug) in the treatment of hyperkalemia (high serum potassium). The study also evaluated the effect of withdrawing patiromer treatment and assessed whether chronic treatment with patiromer prevented the recurrence of hyperkalemia. The safety of patiromer treatment was also evaluated.
Detailed description
There were two parts in the study, Part A and Part B. Part A was an assessment of 4 weeks of dosing with patiromer in the treatment of hyperkalemia; Part B was a randomized, placebo-controlled, 8-week assessment of the withdrawal of patiromer in participants with a baseline serum potassium at the beginning of Part A ≥ 5.5 mEq/L who responded to the 4 weeks of treatment with patiromer during Part A. All participants received patiromer during Part A; Part B participants were randomized to continue patiromer or switch to placebo. Total study participation was up to 14 weeks (including up to 2 weeks of follow up). The dose of patiromer could be titrated based on participant's serum potassium response.
Interventions
DRUGPatiromer
DRUGPlacebo
Sponsors
Relypsa, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Males and females ages 18 - 80 * Chronic kidney disease (CKD) - eGFR 15 to \< 60 mL/min/1.73m2 at screening * Hyperkalemia, defined as a serum potassium value of 5.1 to \< 6.5 mEq/L at screening * Taking either an Angiotensin-Converting Enzyme (ACE) Inhibitor, an Angiotensin II receptor blocker (ARB), or an aldosterone antagonist (AA) medication * Informed consent given
Exclusion criteria
* Participants with auto-immune related chronic kidney disease such as lupus nephritis or renal scleroderma/scleroderma renal crisis, or mixed connective tissue disease with renal involvement * Participants with uncontrolled Type 1 diabetes, defined as or a HbA1c \> 10.0 %, or hospitalization to treat hyper- or hypo-glycemia in the past 3 months within the previous 6 months in participants with Type 2 diabetes * Participants with severe heart failure, defined as NYHA (New York Heart Association) class IV * Participants with major surgery including thoracic and cardiac, in the past 3 months, or participants with heart or kidney transplant * Participants with significant cardiovascular or cerebrovascular events in the past 2 months, such as cardiac arrest, myocardial infarction, or stroke * Participants with BMI ≥ 40 kg/m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Potassium From Part A Baseline to Part A Week 4 | Part A Baseline to Part A Week 4 | The primary analysis endpoint is the change from Baseline at Week 4. The estimate of the change at Week 4 is from a repeated measures model, which includes data from Weeks 1, 2, 3 and 4. The analysis includes all intent to treat participants who had a serum potassium result at baseline and at least one weekly post-baseline visit (i.e. Part A Week 1 or later) and excludes six participants who had no result collected after Day 3). |
| Change in Serum Potassium From Part B Baseline | Part B Baseline to Part B Week 4 or first local laboratory serum potassium < 3.8 mEq/L or ≥ 5.5 mEq/L | Change in Serum Potassium from Part B Baseline to either: Part B Week 4 visit, if the participant's serum potassium remained ≥ 3.8 mEq/L and \< 5.5 mEq/L up to the Part B Week 4 visit or the earliest Part B visit at which the participant's serum potassium was \< 3.8 mEq/L or ≥ 5.5 mEq/L. |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Participants With Serum Potassium Levels in the Target Range of 3.8 to < 5.1 mEq/L at Part A Week 4 | Week 4 |
| Proportion of Participants With Serum Potassium That Was ≥ 5.5 mEq/L in Part B | Part B Baseline to Part B Week 8 |
| Proportion of Participants With Serum Potassium ≥ 5.1 mEq/L in Part B | Part B Baseline to Part B Week 8 |
Countries
Croatia, Czechia, Denmark, Georgia, Hungary, Italy, Serbia, Slovenia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A Patiromer Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks. | 243 |
| Total | 243 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part A Treatment Period | Adverse Event | 10 | 0 | 0 |
| Part A Treatment Period | Non-compliance with Study Drug | 1 | 0 | 0 |
| Part A Treatment Period | Protocol-specified (eGFR) | 2 | 0 | 0 |
| Part A Treatment Period | Protocol-specified (High K+) | 3 | 0 | 0 |
| Part A Treatment Period | Protocol-specified (Low K+) | 1 | 0 | 0 |
| Part A Treatment Period | Protocol Violation | 2 | 0 | 0 |
| Part A Treatment Period | Withdrawal by Subject | 5 | 0 | 0 |
| Part B Placebo-Controlled Withdrawal | Adverse Event | 0 | 1 | 1 |
| Part B Placebo-Controlled Withdrawal | Death | 0 | 0 | 1 |
| Part B Placebo-Controlled Withdrawal | Lost to Follow-up | 0 | 1 | 0 |
| Part B Placebo-Controlled Withdrawal | Non-compliance with Study Drug | 0 | 1 | 0 |
| Part B Placebo-Controlled Withdrawal | Physician Decision | 0 | 1 | 1 |
| Part B Placebo-Controlled Withdrawal | Protocol-specified (eGFR) | 0 | 1 | 1 |
| Part B Placebo-Controlled Withdrawal | Protocol-specified (High K+) | 0 | 2 | 14 |
| Part B Placebo-Controlled Withdrawal | Protocol-specified (K+ result) | 0 | 1 | 2 |
| Part B Placebo-Controlled Withdrawal | Protocol-specified (Low K+) | 0 | 2 | 1 |
| Part B Placebo-Controlled Withdrawal | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part A Patiromer |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 131 Participants |
| Age, Categorical Between 18 and 65 years | 112 Participants |
| Age, Continuous | 64.2 years |
| Sex: Female, Male Female | 103 Participants |
| Sex: Female, Male Male | 140 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 243 | 5 / 55 | 8 / 52 |
| serious Total, serious adverse events | 3 / 243 | 0 / 55 | 1 / 52 |
Outcome results
Primary
Change in Serum Potassium From Part A Baseline to Part A Week 4
The primary analysis endpoint is the change from Baseline at Week 4. The estimate of the change at Week 4 is from a repeated measures model, which includes data from Weeks 1, 2, 3 and 4. The analysis includes all intent to treat participants who had a serum potassium result at baseline and at least one weekly post-baseline visit (i.e. Part A Week 1 or later) and excludes six participants who had no result collected after Day 3).
Time frame: Part A Baseline to Part A Week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A Patiromer | Change in Serum Potassium From Part A Baseline to Part A Week 4 | -1.01 mEq/L | Standard Error 0.031 |
Comparison: Estimation of mean change in serum potassium from Part A Baseline to Part A Week 4 and test mean change different from zero.p-value: <0.001Longitudinal mixed models
Primary
Change in Serum Potassium From Part B Baseline
Change in Serum Potassium from Part B Baseline to either: Part B Week 4 visit, if the participant's serum potassium remained ≥ 3.8 mEq/L and \< 5.5 mEq/L up to the Part B Week 4 visit or the earliest Part B visit at which the participant's serum potassium was \< 3.8 mEq/L or ≥ 5.5 mEq/L.
Time frame: Part B Baseline to Part B Week 4 or first local laboratory serum potassium < 3.8 mEq/L or ≥ 5.5 mEq/L
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A Patiromer | Change in Serum Potassium From Part B Baseline | 0.72 mEq/L |
| Part B Patiromer | Change in Serum Potassium From Part B Baseline | 0 mEq/L |
Comparison: Test for difference between treatment groups in serum potassium change in Part Bp-value: <0.001ANCOVA
Secondary
Proportion of Participants With Serum Potassium ≥ 5.1 mEq/L in Part B
Time frame: Part B Baseline to Part B Week 8
Population: Percentages were estimated not as simple ratios, but by using a stratified method, in order to account for differences between the patiromer and placebo groups in terms of whether participants had type 2 diabetes mellitus and whether they entered the study with serum potassium \< 5.8 mEq/L or serum potassium ≥ 5.8 mEq/L.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Patiromer | Proportion of Participants With Serum Potassium ≥ 5.1 mEq/L in Part B | 91 percentage of participants |
| Part B Patiromer | Proportion of Participants With Serum Potassium ≥ 5.1 mEq/L in Part B | 43 percentage of participants |
Comparison: Test for difference between treatment groups in proportion with serum potassium ≥ 5.1 mEq/Lp-value: <0.001Mantel Haenszel
Secondary
Proportion of Participants With Serum Potassium Levels in the Target Range of 3.8 to < 5.1 mEq/L at Part A Week 4
Time frame: Week 4
Population: Proportion of participants with serum potassium level in the target range at Part A Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Patiromer | Proportion of Participants With Serum Potassium Levels in the Target Range of 3.8 to < 5.1 mEq/L at Part A Week 4 | 76 percentage of participants |
95% CI: [0.7, 0.81]
Secondary
Proportion of Participants With Serum Potassium That Was ≥ 5.5 mEq/L in Part B
Time frame: Part B Baseline to Part B Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Patiromer | Proportion of Participants With Serum Potassium That Was ≥ 5.5 mEq/L in Part B | 60 percentage of participants |
| Part B Patiromer | Proportion of Participants With Serum Potassium That Was ≥ 5.5 mEq/L in Part B | 15 percentage of participants |
Comparison: Test for difference between treatment groups in proportion with serum potassium ≥ 5.5 mEq/Lp-value: <0.001Mantel Haenszel