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The purpose of this study was to evaluate the feasibility of individualized titration of patiromer according to serum potassium. This study also assessed the safety and tolerability of patiromer and the effects of patiromer on serum potassium in heart failure (HF) participants with chronic kidney disease (CKD).
This was an open-label, single-arm study to evaluate a titration regimen for patiromer in approximately 63 HF participants with CKD receiving one or more of the following: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), or beta blockers (BBs). This study was considered to be exploratory.
Upon successful completion of screening evaluations (-10 to -5 days prior to enrollment), all eligible participants were assigned at Baseline (Day 0 visit) to an initial dose of patiromer (20 g/day) and spironolactone (25 mg/day).
Study visits for enrolled participants were scheduled for Days 3, 7, 14, 21, 28, 35, 42, 49 and 56. A follow-up visit occurred on Day 63.
At selected study visits, patiromer or spironolactone doses may have been titrated. The study dosing algorithm was designed to maintain an individual's serum potassium value in the range of 4.0 - 5.1 mEq/L (based on local lab data).
Any participant with a local laboratory serum potassium value < 3.5 or > 5.5 mEq/L on two consecutive scheduled study visits, despite titration of patiromer or spironolactone, were withdrawn from the study, permanently discontinued patiromer and spironolactone, and returned for a follow-up visit within 7 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| patiromer | Experimental | spironolactone + patiromer |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| patiromer | Drug | Active investigational drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment | 56 days |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 4 | 28 Days | |
| Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 8 | 56 Days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Director Clinical Operations | Relypsa, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigator Site 11 | Tbilisi | Georgia | ||||
| Investigator Site 12 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29369537 | Derived | Pitt B, Bushinsky DA, Kitzman DW, Ruschitzka F, Metra M, Filippatos G, Rossignol P, Du Mond C, Garza D, Berman L, Lainscak M; Patiromer-204 Investigators. Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease. ESC Heart Fail. 2018 Jun;5(3):257-266. doi: 10.1002/ehf2.12265. Epub 2018 Jan 25. |
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Eligible participants were ≥ 18 years old, had a history of chronic HF, were clinically indicated to initiate spironolactone therapy, had a serum potassium measurement of 4.3 - 5.1 mEq/L at screening and baseline, had CKD (eGFR < 60 mL/min/1.73 m2 at screening), and were taking one or more HF therapies (ACEIs, ARBs, or BBs).
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| ID | Title | Description |
|---|---|---|
| FG000 | Patiromer | Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Patiromer | Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment | Posted | Number | percentage of participants | 56 days |
|
|
Up to 7 days after Day 56 or last patiromer dose, whichever was earlier.
Participants who received at least one dose of trial medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Patiromer | Spironolactone + Patiromer Participants received patiromer (20 g/day, administered as a divided dose of 10 g in the morning and 10 g in the evening) and spironolactone (25 mg/day, administered once daily), orally. After Day 3, at the first occurrence of a serum potassium value of ≤ 5.1 mEq/L, the spironolactone dose was increased once to 50 mg/day; dose reductions were not allowed. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA 12.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Information | Relypsa, Inc. | 1-844-relypsa | medinfo@relypsa.com |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D006947 | Hyperkalemia |
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014883 | Water-Electrolyte Imbalance |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| C568789 | patiromer |
| D013148 | Spironolactone |
| ID | Term |
|---|---|
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 |
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| spironolactone | Drug |
|
| Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 4 | 28 Days |
| Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 8 | 56 Days |
| Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at the End of Treatment | 56 Days |
| Mean Dose of Patiromer at End of Treatment | 56 Days |
| Percentage of Participants Requiring Patiromer Uptitration | 56 Days |
| Percentage of Participants Requiring Patiromer Downtitration | 56 Days |
| Median Time to First Patiromer Dose Titration | 56 Days |
| Mean Number of Patiromer Titrations | 56 Days |
| Mean Patiromer Dose at Week 1 | Up to Week 1 |
| Mean Patiromer Dose at Week 4 | Up to Week 4 |
| Mean Patiromer Dose at Week 8 | Up to Week 8 |
| Mean Change From Baseline in Serum Potassium to End of Treatment | 56 Days |
| Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L) | 56 Days |
| Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day | 56 Days |
| Change in Urine Albumin to Creatinine Ratio (ACR) From Baseline to Week 4 Among Participants With ACR ≥ 30 mg/g at Baseline | Baseline and Day 28 |
| Change in ACR From Baseline to Week 8 Among Participants With Urine ACR ≥ 30 mg/g at Baseline | Baseline and Day 56 |
| Tbilisi |
| Georgia |
| Investigator Site 13 | Tbilisi | Georgia |
| Investigator Site 14 | Tbilisi | Georgia |
| Investigator Site 15 | Tbilisi | Georgia |
| Investigator Site 16 | Tbilisi | Georgia |
| Investigator Site 17 | Tbilisi | Georgia |
| Investigator Site 18 | Tbilisi | Georgia |
| Investigator Site 25 | Golnik | Slovenia |
| Investigator Site 27 | Izola | Slovenia |
| Investigator Site 21 | Ljubljana | Slovenia |
| Investigator Site 22 | Maribor | Slovenia |
| Investigator Site 26 | Slovenj Gradec | Slovenia |
| Protocol Violation |
|
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 4 | Participants with available data at Week 4. | Posted | Number | percentage of participants | 28 Days |
|
|
|
| Secondary | Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 8 | Participants with available data at Week 8. | Posted | Number | percentage of participants | 56 Days |
|
|
|
| Secondary | Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 4 | Participants with available data at Week 4. | Posted | Number | percentage of participants | 28 Days |
|
|
|
| Secondary | Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 8 | Participants with available data at Week 8. | Posted | Number | percentage of participants | 56 Days |
|
|
|
| Secondary | Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at the End of Treatment | Posted | Number | percentage of participants | 56 Days |
|
|
|
|
| Secondary | Mean Dose of Patiromer at End of Treatment | Posted | Mean | Standard Deviation | grams | 56 Days |
|
|
|
| Secondary | Percentage of Participants Requiring Patiromer Uptitration | Posted | Number | percentage of participants | 56 Days |
|
|
|
| Secondary | Percentage of Participants Requiring Patiromer Downtitration | Posted | Number | percentage of participants | 56 Days |
|
|
|
| Secondary | Median Time to First Patiromer Dose Titration | Posted | Median | 95% Confidence Interval | days | 56 Days |
|
|
|
| Secondary | Mean Number of Patiromer Titrations | Posted | Mean | Standard Deviation | patiromer titrations | 56 Days |
|
|
|
| Secondary | Mean Patiromer Dose at Week 1 | Posted | Mean | Standard Deviation | grams | Up to Week 1 |
|
|
|
| Secondary | Mean Patiromer Dose at Week 4 | Posted | Mean | Standard Deviation | grams | Up to Week 4 |
|
|
|
| Secondary | Mean Patiromer Dose at Week 8 | Posted | Mean | Standard Deviation | grams | Up to Week 8 |
|
|
|
| Secondary | Mean Change From Baseline in Serum Potassium to End of Treatment | Posted | Mean | Standard Deviation | mEq/L | 56 Days |
|
|
|
| Secondary | Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L) | Posted | Number | percentage of participants | 56 Days |
|
|
|
| Secondary | Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day | Posted | Number | percentage of participants | 56 Days |
|
|
|
| Secondary | Change in Urine Albumin to Creatinine Ratio (ACR) From Baseline to Week 4 Among Participants With ACR ≥ 30 mg/g at Baseline | Participants with urine ACR ≥ 30 mg/g at baseline and available data at Week 4 | Posted | Mean | Standard Error | mg/g | Baseline and Day 28 |
|
|
|
| Secondary | Change in ACR From Baseline to Week 8 Among Participants With Urine ACR ≥ 30 mg/g at Baseline | Participants with urine ACR ≥ 30 mg/g at baseline and available data at Week 8 | Posted | Mean | Standard Error | mg/g | Baseline and Day 56 |
|
|
|
| 6 |
| 63 |
| 4 |
| 63 |
| Sudden cardiac death | General disorders | MedDRA 12.0 | Systematic Assessment |
|
| Sudden death | General disorders | MedDRA 12.0 | Systematic Assessment | Sudden death occurred during the follow up period, after completing the study. |
|
| Pneumonia | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
|
| Staphylococcal sepsis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
|
| Subcutaneous abscess | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
|
| Azotaemia | Renal and urinary disorders | MedDRA 12.0 | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA 12.0 | Systematic Assessment |
|
Our agreements generally provide that PI cannot publish single site data before publication of the multi-site publication, unless 1 year has elapsed since completion of the study at all sites. Thereafter, PI may publish provided that PI shall: provide a copy of the publication to sponsor at least 60 days in advance of submission for publication; delete sponsor's confidential information as requested; and delay publication up to an additional 90 days to permit protection of intellectual property.
| D009750 |
| Nutritional and Metabolic Diseases |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |