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

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ClinicalTrials.gov Identifier: NCT01130597
Recruitment Status : Completed
First Posted : May 26, 2010
Results First Posted : January 28, 2016
Last Update Posted : January 28, 2016
Sponsor:
Information provided by (Responsible Party):
Relypsa, Inc.

Tracking Information
First Submitted Date  ICMJE May 24, 2010
First Posted Date  ICMJE May 26, 2010
Results First Submitted Date  ICMJE November 11, 2015
Results First Posted Date  ICMJE January 28, 2016
Last Update Posted Date January 28, 2016
Study Start Date  ICMJE May 2010
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 21, 2015)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 24, 2010)
Proportion of patients with serum potassium in the normal range of 3.5 - 5.5 mEq/L at the end of the study [ Time Frame: 64 days ]
Change History Complete list of historical versions of study NCT01130597 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2015)
  • Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 4 [ Time Frame: 28 Days ]
  • Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 8 [ Time Frame: 56 Days ]
  • Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 4 [ Time Frame: 28 Days ]
  • Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 8 [ Time Frame: 56 Days ]
  • 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 ]
  • Mean Dose of Patiromer at End of Treatment [ Time Frame: 56 Days ]
  • Percentage of Participants Requiring Patiromer Uptitration [ Time Frame: 56 Days ]
  • Percentage of Participants Requiring Patiromer Downtitration [ Time Frame: 56 Days ]
  • Median Time to First Patiromer Dose Titration [ Time Frame: 56 Days ]
  • Mean Number of Patiromer Titrations [ Time Frame: 56 Days ]
  • Mean Patiromer Dose at Week 1 [ Time Frame: Up to Week 1 ]
  • Mean Patiromer Dose at Week 4 [ Time Frame: Up to Week 4 ]
  • Mean Patiromer Dose at Week 8 [ Time Frame: Up to Week 8 ]
  • Mean Change From Baseline in Serum Potassium to End of Treatment [ Time Frame: 56 Days ]
  • Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L) [ Time Frame: 56 Days ]
  • Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day [ Time Frame: 56 Days ]
  • 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 ]
  • Change in ACR From Baseline to Week 8 Among Participants With Urine ACR ≥ 30 mg/g at Baseline [ Time Frame: Baseline and Day 56 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Patiromer Titration in Heart Failure Patients With Chronic Kidney Disease
Official Title  ICMJE A Multicenter, Open-Label, Single-Arm Study to Evaluate a Titration Regimen for Patiromer in Heart Failure Patients With Chronic Kidney Disease
Brief Summary 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).
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Heart Failure
Intervention  ICMJE
  • Drug: patiromer
    Active investigational drug
    Other Names:
    • RLY5016
    • Veltassa
  • Drug: spironolactone
Study Arms  ICMJE Experimental: patiromer
spironolactone + patiromer
Interventions:
  • Drug: patiromer
  • Drug: spironolactone
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 6, 2011)
63
Original Estimated Enrollment  ICMJE
 (submitted: May 24, 2010)
60
Actual Study Completion Date  ICMJE September 2010
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Georgia,   Slovenia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01130597
Other Study ID Numbers  ICMJE RLY5016-204
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Relypsa, Inc.
Study Sponsor  ICMJE Relypsa, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Director Clinical Operations Relypsa, Inc.
PRS Account Relypsa, Inc.
Verification Date December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP