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Evaluation of Patiromer Titration in Heart Failure Patients With Chronic Kidney Disease

This study has been completed.
Information provided by (Responsible Party):
Relypsa, Inc. Identifier:
First received: May 24, 2010
Last updated: December 21, 2015
Last verified: December 2015
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).

Condition Intervention Phase
Heart Failure
Drug: patiromer
Drug: spironolactone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Multicenter, Open-Label, Single-Arm Study to Evaluate a Titration Regimen for Patiromer in Heart Failure Patients With Chronic Kidney Disease

Resource links provided by NLM:

Further study details as provided by Relypsa, Inc.:

Primary Outcome Measures:
  • Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment [ Time Frame: 56 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 4 [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
  • Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 8 [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 4 [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
  • Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 8 [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at the End of Treatment [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Mean Dose of Patiromer at End of Treatment [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Percentage of Participants Requiring Patiromer Uptitration [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Percentage of Participants Requiring Patiromer Downtitration [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Median Time to First Patiromer Dose Titration [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Mean Number of Patiromer Titrations [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Mean Patiromer Dose at Week 1 [ Time Frame: Up to Week 1 ] [ Designated as safety issue: No ]
  • Mean Patiromer Dose at Week 4 [ Time Frame: Up to Week 4 ] [ Designated as safety issue: No ]
  • Mean Patiromer Dose at Week 8 [ Time Frame: Up to Week 8 ] [ Designated as safety issue: No ]
  • Mean Change From Baseline in Serum Potassium to End of Treatment [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L) [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day [ Time Frame: 56 Days ] [ Designated as safety issue: No ]
  • Change in Urine Albumin to Creatinine Ratio (ACR) From Baseline to Week 4 Among Participants With ACR ≥ 30 mg/g at Baseline [ Time Frame: Baseline and Day 28 ] [ Designated as safety issue: No ]
  • Change in ACR From Baseline to Week 8 Among Participants With Urine ACR ≥ 30 mg/g at Baseline [ Time Frame: Baseline and Day 56 ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: May 2010
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: patiromer
spironolactone + patiromer
Drug: patiromer
Active investigational drug
Other Names:
  • RLY5016
  • Veltassa
Drug: spironolactone

Detailed Description:

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Chronic HF clinically indicated to receive spironolactone therapy
  2. Age 18 years or older
  3. Local laboratory serum potassium values of 4.3 - 5.1 mEq/L at screening and baseline
  4. CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2 at screening based on central lab creatinine measurement)
  5. On at least one of the following HF therapies: ACEI, ARB, or BB
  6. 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 study drug administration, during the study, and for one month after study completion
  7. Male participants and/or their female partners of child-bearing potential must use a highly effective form of contraception during the study and for 3 months after study completion
  8. Provide their written informed consent prior to participation in the study

Exclusion Criteria:

  1. History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery
  2. Uncorrected primary severe valvular disease, known obstructive or restrictive cardiomyopathy, uncontrolled or hemodynamically unstable arrhythmia
  3. Coronary-artery bypass graft, percutaneous intervention (e.g., cardiac, cerebrovascular, aortic), or major surgery including thoracic and cardiac, within 3 months prior to baseline or anticipated need during study participation
  4. Heart transplant recipient, or anticipated need for transplant during study participation
  5. Any of the following events having occurred within 2 months prior to baseline: unstable angina as judged by the Investigator, unresolved acute coronary syndrome, transient ischemic attack or stroke
  6. Current dialysis participant, or anticipated need for dialysis during study participation
  7. Prior kidney transplant, or anticipated need for transplant during study participation
  8. Metastatic, late-stage or end-stage cancer with < 12 months life expectancy or at risk for tumor lysis syndrome
  9. History of alcoholism or drug/chemical abuse within 1 year
  10. Sustained systolic blood pressure > 180 or < 90 mmHg
  11. Liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] > 3 times upper limit of normal
  12. Loop and thiazide diuretics that have not been stable for at least 21 days prior to baseline or not anticipated to remain stable during study participation
  13. Use of any intravenous cardiac medications within 21 days prior to baseline, or their anticipated need during study participation
  14. Current use of polymer-based drugs (e.g., sevelamer, sodium polystyrene sulfonate, colesevelam, colestipol), phosphate binders (e.g., lanthanum carbonate), or other potassium binders, or their anticipated need during study participation
  15. Use of potassium sparing medication including aldosterone antagonists or potassium supplements in the last 21 days prior to baseline
  16. Use of any investigational medication within 30 days or 5 half-lives, whichever is longer, prior to baseline
  17. Participants who have taken investigational product in this study, or a previous patiromer study
  18. Inability to consume the study medication, or, in the opinion of the Investigator, inability to comply with the protocol
  19. In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, serious intercurrent illness, or extenuating circumstance occurring or persisting, within 30 days prior to baseline, that would significantly decrease study compliance or jeopardize the safety of the participant or affect the validity of the trial results
  Contacts and Locations
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Please refer to this study by its identifier: NCT01130597

Investigator Site 11
Tbilisi, Georgia
Investigator Site 12
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
Sponsors and Collaborators
Relypsa, Inc.
Study Director: Director Clinical Operations Relypsa, Inc.
  More Information

Additional Information:
Responsible Party: Relypsa, Inc. Identifier: NCT01130597     History of Changes
Other Study ID Numbers: RLY5016-204 
Study First Received: May 24, 2010
Results First Received: November 11, 2015
Last Updated: December 21, 2015
Health Authority: Slovenia: Agency for Medicinal Products - Ministry of Health
Georgia: Ministry of Health
Slovenia: Ethics Committee

Keywords provided by Relypsa, Inc.:
Heart failure
chronic kidney disease
prevention of hyperkalemia in heart failure participants

Additional relevant MeSH terms:
Heart Failure
Kidney Diseases
Renal Insufficiency, Chronic
Heart Diseases
Cardiovascular Diseases
Urologic Diseases
Renal Insufficiency
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents processed this record on January 14, 2017